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Article ; Online: Response to article - alternative interpretation of "there is reduced immunohistochemical staining of placental aromatase in severe neonatal opioid withdrawal syndrome".

Tobacyk, Julia / Brents, Lisa K

The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians

2023 Volume 36, Issue 1, Page(s) 2183469

MeSH term(s)	Female ; Pregnancy ; Infant, Newborn ; Humans ; Aromatase ; Analgesics, Opioid/adverse effects ; Placenta
Chemical Substances	Aromatase (EC 1.14.14.1) ; Analgesics, Opioid
Language	English
Publishing date	2023-03-02
Publishing country	England
Document type	Letter ; Comment
ZDB-ID	2077261-0
ISSN	1476-4954 ; 1057-0802 ; 1476-7058
ISSN (online)	1476-4954
ISSN	1057-0802 ; 1476-7058
DOI	10.1080/14767058.2023.2183469
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Article ; Online: Limited bedding and nesting increases ethanol drinking in female rats.

Parks, B J / Salazar, P / Morrison, L / McGraw, M K / Gunnell, M / Tobacyk, J / Brents, L K / Berquist, M D

Pharmacology, biochemistry, and behavior

2024 Volume 239, Page(s) 173756

Abstract: Prenatal opioid exposure (POE) and postnatal adverse experiences are early life adversities (ELA) that often co-occur and increase problematic alcohol (EtOH) drinking during adolescence. We investigated the relationship between POE, postnatal adversity, ... ...

Abstract	Prenatal opioid exposure (POE) and postnatal adverse experiences are early life adversities (ELA) that often co-occur and increase problematic alcohol (EtOH) drinking during adolescence. We investigated the relationship between POE, postnatal adversity, and adolescent EtOH drinking in rats. We also sought to determine whether ELAs affect alpha-adrenoceptor density in the brain because the noradrenergic system is involved in problematic alcohol drinking and its treatment. We hypothesized that the combination of POE and postnatal adversity will increase alcohol drinking in rats compared to rats with exposure to either adversity alone or to control. We also predicted that POE and postnatal adversity would increase α
MeSH term(s)	Animals ; Female ; Rats ; Pregnancy ; Alcohol Drinking/metabolism ; Prenatal Exposure Delayed Effects/metabolism ; Ethanol/administration & dosage ; Ethanol/pharmacology ; Male ; Receptors, Adrenergic, alpha-2/metabolism ; Morphine/pharmacology ; Brain/metabolism ; Brain/drug effects ; Receptors, Adrenergic, alpha-1/metabolism ; Rats, Sprague-Dawley
Chemical Substances	Ethanol (3K9958V90M) ; Receptors, Adrenergic, alpha-2 ; Morphine (76I7G6D29C) ; Receptors, Adrenergic, alpha-1
Language	English
Publishing date	2024-03-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	191042-5
ISSN	1873-5177 ; 0091-3057
ISSN (online)	1873-5177
ISSN	0091-3057
DOI	10.1016/j.pbb.2024.173756
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Article ; Online: Fluorescence-Based Assay For Measuring OMA1 Activity.

Tobacyk, Julia / MacMillan-Crow, Lee Ann

Methods in molecular biology (Clifton, N.J.)

2021 Volume 2276, Page(s) 325–332

Abstract: Mitochondrial fusion depends on proteolytic processing of the dynamin-related GTPase protein, OPA1, which is regulated by the mitochondrial zinc metalloproteinase, OMA1. Last year we published a report describing a novel approach to directly measure the ... ...

Abstract	Mitochondrial fusion depends on proteolytic processing of the dynamin-related GTPase protein, OPA1, which is regulated by the mitochondrial zinc metalloproteinase, OMA1. Last year we published a report describing a novel approach to directly measure the enzymatic activity of OMA1 in whole cell lysates. This fluorescence-based reporter assay utilizes an eight amino acid peptide sequence referred to as the S1 cleavage site where OMA1 cleaves within OPA1 and is flanked by a fluorophore and quencher. In this chapter, we provide additional insight into the OMA1 activity assay.
MeSH term(s)	Cells, Cultured ; Enzyme Assays/methods ; Fluorescent Dyes/chemistry ; GTP Phosphohydrolases/metabolism ; Humans ; Metalloendopeptidases/metabolism ; Mitochondria/enzymology ; Mitochondrial Dynamics ; Peptides/chemistry
Chemical Substances	Fluorescent Dyes ; Peptides ; Metalloendopeptidases (EC 3.4.24.-) ; molecule metalloprotease-related protein-1, human (EC 3.4.24.-) ; GTP Phosphohydrolases (EC 3.6.1.-) ; OPA1 protein, human (EC 3.6.1.-)
Language	English
Publishing date	2021-05-31
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1266-8_24
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Article ; Online: Qualitative content analysis of public responses to an FDA inquiry on the impact of scheduling changes to kratom.

Tobacyk, Julia / Parks, Brian J / Lovelady, Nakita / Brents, Lisa K

The International journal on drug policy

2022 Volume 108, Page(s) 103817

Abstract: Background: The legal status of kratom in the United States is complex and varies by state. The U.S. Food and Drug Administration (FDA) and the U.S. Drug Enforcement Administration have repeatedly subjected kratom to regulatory review. However, there ... ...

Abstract	Background: The legal status of kratom in the United States is complex and varies by state. The U.S. Food and Drug Administration (FDA) and the U.S. Drug Enforcement Administration have repeatedly subjected kratom to regulatory review. However, there hasn't been a systematic review of the public's perception of kratom. The present study analyzed open-ended responses from the public to an FDA solicitation for information regarding kratom with the goal of providing a comprehensive assessment of motives for kratom use. Methods: To guide decisions regarding kratom regulation, the FDA solicited comments regarding kratom abuse potential, medical usefulness, and impact of scheduling changes from July through August 2021 and posted them to the Federal Register website. We analyzed comments posted during the first 6 weeks of comment solicitation (6,353) using an inductive approach via qualitative content analysis. Results: Respondents reported 106 independent health-related reasons for kratom use, with most categorized as mental health, pain management, substance use disorder, or miscellaneous purposes that included increasing focus, treating insomnia, and decreasing fatigue. Neurological diseases and digestive disorders were also reported. Relatively few (< 2%) responses reported recreational use, abuse potential, or adverse effects of kratom. Conclusions: Although kratom is not approved as a safe and effective therapy for any indication, individuals use kratom for a broad spectrum of health-related purposes. Limitations of this study include potential bias for respondents with perceived positive experiences using kratom, lack of demographics data, and lack of independent verification of claims made by respondents. Regardless, this study reflects perceptions regarding the therapeutic uses of kratom and provides insight into potential individual-level consequences of regulating kratom in the U.S. It is important to study the public's perception of kratom use, which can aid regulatory purposes and provide clinically important information on individuals' use and valuation of kratom.
MeSH term(s)	Humans ; Mitragyna/adverse effects ; Pain Management ; Substance-Related Disorders ; United States ; United States Food and Drug Administration
Language	English
Publishing date	2022-08-08
Publishing country	Netherlands
Document type	Journal Article ; Systematic Review ; Research Support, N.I.H., Extramural
ZDB-ID	2010000-0
ISSN	1873-4758 ; 0955-3959
ISSN (online)	1873-4758
ISSN	0955-3959
DOI	10.1016/j.drugpo.2022.103817
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Article: Overexpression of MnSOD Protects against Cold Storage-Induced Mitochondrial Injury but Not against OMA1-Dependent OPA1 Proteolytic Processing in Rat Renal Proximal Tubular Cells.

Tobacyk, Julia / Kc, Grishma / MacMillan-Crow, Lee Ann

Antioxidants (Basel, Switzerland)

2021 Volume 10, Issue 8

Abstract: Kidneys from deceased donors undergo cold storage (CS) preservation before transplantation. Although CS is a clinical necessity for extending organ quality preservation, CS causes mitochondrial and renal injury. Specifically, many studies, including our ... ...

Abstract	Kidneys from deceased donors undergo cold storage (CS) preservation before transplantation. Although CS is a clinical necessity for extending organ quality preservation, CS causes mitochondrial and renal injury. Specifically, many studies, including our own, have shown that the triggering event of CS-induced renal injury is mitochondrial reactive oxygen species (mROS). Here, we explored the role of OMA1-depedent OPA1 proteolytic processing in rat kidney proximal tubular epithelial (NRK) cells in an in vitro model of renal CS (18 h), followed by rewarming (6 h) (CS + RW). The involvement of mROS was evaluated by stably overexpressing manganese superoxide dismutase (MnSOD), an essential mitochondrial antioxidant enzyme, in NRK cells. Western blots detected rapid OPA1 proteolytic processing and a decrease in ATP-dependent cell viability in NRK cells subjected to CS + RW compared to control cells. Small interfering RNA (siRNA) knockdown of OMA1 reduced proteolytic processing of OPA1, suggesting that OMA1 is responsible for OPA1 proteolytic processing during CS + RW-induced renal injury. Overexpression of MnSOD during CS + RW reduced cell death, mitochondrial respiratory dysfunction, and ATP-dependent cell viability, but it did not prevent OMA1-dependent OPA1 processing. These data show for the first time that OMA1 is responsible for proteolytically cleaving OPA1 in a redox-independent manner during renal cell CS.
Language	English
Publishing date	2021-08-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10081272
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Article ; Online: Interaction between buprenorphine and norbuprenorphine in neonatal opioid withdrawal syndrome.

Tobacyk, Julia / Parks, Brian J / Salazar, Paloma / Coward, Lori U / Berquist, Michael D / Gorman, Gregory S / Brents, Lisa K

Drug and alcohol dependence

2023 Volume 249, Page(s) 110832

Abstract: Buprenorphine (BUP) is the preferred treatment for opioid use disorder during pregnancy but can cause neonatal opioid withdrawal syndrome (NOWS). Norbuprenorphine (NorBUP), an active metabolite of BUP, is implicated in BUP-associated NOWS. We ... ...

Abstract	Buprenorphine (BUP) is the preferred treatment for opioid use disorder during pregnancy but can cause neonatal opioid withdrawal syndrome (NOWS). Norbuprenorphine (NorBUP), an active metabolite of BUP, is implicated in BUP-associated NOWS. We hypothesized that BUP, a low-efficacy agonist of mu opioid receptors, will not antagonize NorBUP, a high-efficacy agonist of mu opioid receptors, in producing NOWS. To test this hypothesis, we treated pregnant Long-Evans rats with BUP (0, 0.01, 0.1 or 1mg/kg/day) ± NorBUP (1mg/kg/day) from gestation day 9 until pup delivery, and tested pups for opioid dependence using our established NOWS model. We used LC-MS-MS to quantify brain concentrations of BUP, NorBUP, and their glucuronide conjugates. BUP had little effect on NorBUP-induced NOWS, with the exception of 1mg/kg/day BUP significantly increasing NorBUP-induced NOWS by 58% in females. BUP and NorBUP brain concentrations predicted NOWS in multiple linear regression models. Interestingly, NorBUP contributed more to NOWS in females (β
MeSH term(s)	Humans ; Male ; Animals ; Rats ; Pregnancy ; Female ; Infant, Newborn ; Analgesics, Opioid/therapeutic use ; Receptors, Opioid, mu ; Rats, Long-Evans ; Buprenorphine ; Opioid-Related Disorders/drug therapy ; Neonatal Abstinence Syndrome
Chemical Substances	norbuprenorphine (7E53B4O073) ; Analgesics, Opioid ; Receptors, Opioid, mu ; Buprenorphine (40D3SCR4GZ)
Language	English
Publishing date	2023-06-21
Publishing country	Ireland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	519918-9
ISSN	1879-0046 ; 0376-8716
ISSN (online)	1879-0046
ISSN	0376-8716
DOI	10.1016/j.drugalcdep.2023.110832
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Article: Overexpression of MnSOD Protects against Cold Storage-Induced Mitochondrial Injury but Not against OMA1-Dependent OPA1 Proteolytic Processing in Rat Renal Proximal Tubular Cells

Tobacyk, Julia / KC, Grishma / MacMillan-Crow, Lee Ann

Antioxidants. 2021 Aug. 11, v. 10, no. 8

2021

Abstract	Kidneys from deceased donors undergo cold storage (CS) preservation before transplantation. Although CS is a clinical necessity for extending organ quality preservation, CS causes mitochondrial and renal injury. Specifically, many studies, including our own, have shown that the triggering event of CS-induced renal injury is mitochondrial reactive oxygen species (mROS). Here, we explored the role of OMA1-depedent OPA1 proteolytic processing in rat kidney proximal tubular epithelial (NRK) cells in an in vitro model of renal CS (18 h), followed by rewarming (6 h) (CS + RW). The involvement of mROS was evaluated by stably overexpressing manganese superoxide dismutase (MnSOD), an essential mitochondrial antioxidant enzyme, in NRK cells. Western blots detected rapid OPA1 proteolytic processing and a decrease in ATP-dependent cell viability in NRK cells subjected to CS + RW compared to control cells. Small interfering RNA (siRNA) knockdown of OMA1 reduced proteolytic processing of OPA1, suggesting that OMA1 is responsible for OPA1 proteolytic processing during CS + RW-induced renal injury. Overexpression of MnSOD during CS + RW reduced cell death, mitochondrial respiratory dysfunction, and ATP-dependent cell viability, but it did not prevent OMA1-dependent OPA1 processing. These data show for the first time that OMA1 is responsible for proteolytically cleaving OPA1 in a redox-independent manner during renal cell CS.
Keywords	antioxidant enzymes ; cell death ; cell viability ; cold ; cold storage ; epithelium ; kidneys ; mitochondria ; models ; proteolysis ; rats ; reactive oxygen species ; superoxide dismutase
Language	English
Dates of publication	2021-0811
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10081272
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The BK activator NS11021 partially protects rat kidneys from cold storage and transplantation-induced mitochondrial and renal injury.

Shrum, Stephen / Tobacyk, Julia / Lo, Sorena / Parajuli, Nirmala / MacMillan-Crow, Lee Ann

Archives of biochemistry and biophysics

2020 Volume 688, Page(s) 108410

Abstract: Kidneys from deceased donors used for transplantation are placed in cold storage (CS) solution during the search for a matched recipient. However, CS induces mitochondrial and cellular injury, which exacerbates renal graft dysfunction, highlighting the ... ...

Abstract	Kidneys from deceased donors used for transplantation are placed in cold storage (CS) solution during the search for a matched recipient. However, CS induces mitochondrial and cellular injury, which exacerbates renal graft dysfunction, highlighting the need for therapeutic interventions. Using an in vitro model of renal CS, we recently reported that pharmacological activation of the mitochondrial BK channel (mitoBK) during CS protected against CS-induced mitochondrial injury and cell death. Here, we used an in vivo syngeneic rat model of renal CS (18 h) followed by transplantation (24 h reperfusion) (CS + Tx) to similarly evaluate whether addition of a mitoBK activator to the CS solution can alleviate CS + Tx-induced renal injury. Western blots detected the pore-forming α subunit of the BK channel in mitochondrial fractions from rat kidneys, and mitoBK protein level was reduced after CS + Tx compared to sham surgery. The addition of the BK activator NS11021 (3 μM) to the CS solution partially protected against CS + Tx-induced mitochondrial respiratory dysfunction, oxidative protein nitration, and cell death, but not acute renal dysfunction (SCr and BUN). In summary, the current preclinical study shows that pharmacologically targeting mitoBK channels during CS may be a promising therapeutic intervention to prevent CS + Tx-induced mitochondrial and renal injury.
MeSH term(s)	Animals ; Cell Death/drug effects ; Cryopreservation ; Kidney/drug effects ; Kidney/metabolism ; Kidney/pathology ; Kidney Transplantation/adverse effects ; Large-Conductance Calcium-Activated Potassium Channels/agonists ; Large-Conductance Calcium-Activated Potassium Channels/metabolism ; Male ; Mitochondria/drug effects ; Mitochondria/metabolism ; Rats ; Tetrazoles/pharmacology ; Thiourea/analogs & derivatives ; Thiourea/pharmacology
Chemical Substances	1-(3,5-bis(trifluoromethyl)phenyl)-3-(4-bromo-2-(1H-tetrazol-5-yl)phenyl)thiourea ; Large-Conductance Calcium-Activated Potassium Channels ; Tetrazoles ; Thiourea (GYV9AM2QAG)
Language	English
Publishing date	2020-05-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	523-x
ISSN	1096-0384 ; 0003-9861
ISSN (online)	1096-0384
ISSN	0003-9861
DOI	10.1016/j.abb.2020.108410
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Article: Paranormal beliefs of Latvian college students: a Latvian version of the revised paranormal belief scale.

Utinans, A / Ancane, G / Tobacyk, J J / Boyraz, G / Livingston, M M / Tobacyk, J S

Psychological reports

2015 Volume 116, Issue 1, Page(s) 116–126

Abstract: A Latvian version of the Revised Paranormal Belief Scale (RPBS) was completed by 229 Latvian university students. Exploratory and confirmatory factor analyses revealed six relatively independent factors labeled Magical Abilities, Psychokinesis, ... ...

Abstract	A Latvian version of the Revised Paranormal Belief Scale (RPBS) was completed by 229 Latvian university students. Exploratory and confirmatory factor analyses revealed six relatively independent factors labeled Magical Abilities, Psychokinesis, Traditional Religious Belief, Superstition, Spirit Travel, and Extraordinary Life Forms. Based on the motivational-control model, it was hypothesized that the societal stressors affecting Latvian society during the last 50 yr. have led to a reduced sense of personal control which, in turn, has resulted in increased endorsement of paranormal beliefs to re-establish a sense of control. The motivational-control hypothesis was not supported. Results indicated that (except for Traditional Religious Belief in women), the majority of these students were disbelievers in paranormal phenomena. As hypothesized, Latvian women reported significantly greater paranormal belief than men.
MeSH term(s)	Adult ; Female ; Humans ; Latvia/ethnology ; Male ; Psychometrics/instrumentation ; Students/psychology ; Superstitions/psychology ; Surveys and Questionnaires/standards ; Universities ; Young Adult
Language	English
Publishing date	2015-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	205658-6
ISSN	1558-691X ; 0033-2941
ISSN (online)	1558-691X
ISSN	0033-2941
DOI	10.2466/08.17.PR0.116k14w9
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Article ; Online: The first direct activity assay for the mitochondrial protease OMA1.

Tobacyk, Julia / Parajuli, Nirmala / Shrum, Stephen / Crow, John P / MacMillan-Crow, Lee Ann

Mitochondrion

2019 Volume 46, Page(s) 1–5

Abstract: Mitochondria continually undergo fission and fusion which allow mitochondria to rapidly change their shape, size, and function throughout the cell life cycle. OMA1, a zinc metalloproteinase enzyme, is a key regulator of the mitochondrial fusion machinery. ...

Abstract	Mitochondria continually undergo fission and fusion which allow mitochondria to rapidly change their shape, size, and function throughout the cell life cycle. OMA1, a zinc metalloproteinase enzyme, is a key regulator of the mitochondrial fusion machinery. The paucity of information regarding OMA1 regulation and function largely stems from the fact that there is no direct method to quantitatively measure its activity. Using a fluorescence-based reporter assay, we developed a sensitive method to measure OMA1 enzymatic activity in whole cell lysates.
MeSH term(s)	Animals ; Fluorometry/methods ; Humans ; Metalloendopeptidases/analysis ; Mitochondrial Proteins/analysis
Chemical Substances	Mitochondrial Proteins ; Metalloendopeptidases (EC 3.4.24.-) ; molecule metalloprotease-related protein-1, human (EC 3.4.24.-)
Language	English
Publishing date	2019-03-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2056923-3
ISSN	1872-8278 ; 1567-7249
ISSN (online)	1872-8278
ISSN	1567-7249
DOI	10.1016/j.mito.2019.03.001
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