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Article ; Online: Importin-11 keeps PTEN safe from harm.

Leslie, Nick R

2017 Volume 216, Issue 3, Page(s) 539–541

Abstract: In this issue, Chen et al. (2017. ...

Abstract	In this issue, Chen et al. (2017.
MeSH term(s)	Animals ; Cell Nucleus/metabolism ; Humans ; PTEN Phosphohydrolase/metabolism ; Tumor Suppressor Proteins/metabolism ; beta Karyopherins/metabolism
Chemical Substances	Tumor Suppressor Proteins ; beta Karyopherins ; PTEN Phosphohydrolase (EC 3.1.3.67)
Language	English
Publishing date	2017-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218154-x
ISSN	1540-8140 ; 0021-9525
ISSN (online)	1540-8140
ISSN	0021-9525
DOI	10.1083/jcb.201612014
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Article ; Online: Proteomic and yeast 2-hybrid screens to identify PTEN binding partners.

Tibarewal, Priyanka / Spinelli, Laura / Maccario, Helene / Leslie, Nick R

Advances in biological regulation

2023 Volume 91, Page(s) 100989

Abstract: PTEN is a phosphoinositide lipid phosphatase and an important tumour suppressor protein. PTEN function is reduced or lost in around a third of all human cancers through diverse mechanisms, from gene deletion to changes in the function of proteins which ... ...

Abstract	PTEN is a phosphoinositide lipid phosphatase and an important tumour suppressor protein. PTEN function is reduced or lost in around a third of all human cancers through diverse mechanisms, from gene deletion to changes in the function of proteins which regulate PTEN through direct protein binding. Here we present data from SILAC (Stable Isotope Labelling by Amino acids in Cell culture) proteomic screens to identify proteins which bind to PTEN. These experiments using untransformed epithelial cells and glioma cells identified several novel candidate proteins in addition to many previously identified PTEN binding partners and many proteins which are recognised as common false positives using these methods. From subsequent co-expression pull-down experiments we provide further evidence supporting the physical interaction of PTEN with MMP1, Myosin 18A and SHROOM3. We also performed yeast two-hybrid screens which identify the previously recognised PTEN binding partner MSP58 in addition to the nuclear import export receptor TNPO3. These experiments identify several novel candidate binding partners of PTEN and provide further data addressing the set of proteins that interact with this important tumour suppressor.
MeSH term(s)	Humans ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/metabolism ; Proteomics ; PTEN Phosphohydrolase/genetics ; PTEN Phosphohydrolase/metabolism ; Genes, Tumor Suppressor ; Proteins/genetics ; Neoplasms/genetics ; Protein Binding ; beta Karyopherins/genetics ; beta Karyopherins/metabolism
Chemical Substances	PTEN Phosphohydrolase (EC 3.1.3.67) ; Proteins ; PTEN protein, human (EC 3.1.3.67) ; TNPO3 protein, human ; beta Karyopherins
Language	English
Publishing date	2023-10-04
Publishing country	England
Document type	Journal Article
ZDB-ID	2667413-0
ISSN	2212-4934 ; 2212-4926
ISSN (online)	2212-4934
ISSN	2212-4926
DOI	10.1016/j.jbior.2023.100989
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Article ; Online: Mesna Improves Outcomes of Sulfur Mustard Inhalation Toxicity in an Acute Rat Model.

Nick, Heidi J / Johnson, Carly A / Stewart, Amber R / Christeson, Sarah E / Bloomquist, Leslie A / Appel, Amanda S / Donkor, Abigail B / Veress, Livia A / Logue, Brian A / Bratcher, Preston E / White, Carl W

The Journal of pharmacology and experimental therapeutics

2024 Volume 388, Issue 2, Page(s) 576–585

Abstract: Inhalation of high levels of sulfur mustard (SM), a potent vesicating and alkylating agent used in chemical warfare, results in acutely lethal pulmonary damage. Sodium 2-mercaptoethane sulfonate (mesna) is an organosulfur compound that is currently Food ... ...

Abstract	Inhalation of high levels of sulfur mustard (SM), a potent vesicating and alkylating agent used in chemical warfare, results in acutely lethal pulmonary damage. Sodium 2-mercaptoethane sulfonate (mesna) is an organosulfur compound that is currently Food and Drug Administration (FDA)-approved for decreasing the toxicity of mustard-derived chemotherapeutic alkylating agents like ifosfamide and cyclophosphamide. The nucleophilic thiol of mesna is a suitable reactant for the neutralization of the electrophilic group of toxic mustard intermediates. In a rat model of SM inhalation, treatment with mesna (three doses: 300 mg/kg intraperitoneally 20 minutes, 4 hours, and 8 hours postexposure) afforded 74% survival at 48 hours, compared with 0% survival at less than 17 hours in the untreated and vehicle-treated control groups. Protection from cardiopulmonary failure by mesna was demonstrated by improved peripheral oxygen saturation and increased heart rate through 48 hours. Additionally, mesna normalized arterial pH and pACO
MeSH term(s)	Rats ; Animals ; Mustard Gas/toxicity ; Mesna/pharmacology ; Mesna/therapeutic use ; Antidotes/pharmacology ; Antidotes/therapeutic use ; Lung ; Sodium ; Chemical Warfare Agents/toxicity
Chemical Substances	Mustard Gas (T8KEC9FH9P) ; Mesna (NR7O1405Q9) ; Antidotes ; Sodium (9NEZ333N27) ; Chemical Warfare Agents
Language	English
Publishing date	2024-01-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
DOI	10.1124/jpet.123.001683
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Article ; Online: PTEN: an intercellular peacekeeper?

Leslie, Nick R

Science signaling

2012 Volume 5, Issue 250, Page(s) pe50

Abstract: It is generally assumed that cells synthesize their own intracellular enzymes. Therefore, if expression of a specific gene is silenced in a potential cancer cell, it is expected that loss of protein function will follow. A provocative study indicates an ... ...

Abstract	It is generally assumed that cells synthesize their own intracellular enzymes. Therefore, if expression of a specific gene is silenced in a potential cancer cell, it is expected that loss of protein function will follow. A provocative study indicates an unexpected mechanism of intercellular tumor suppression, showing that PTEN (phosphatase and tensin homolog deleted from chromosome 10), a cytosolic enzyme, can be transferred between cells in exosomes to suppress signaling and proliferation in target cells.
MeSH term(s)	Animals ; Cell Proliferation ; Exosomes/metabolism ; Humans ; Neoplasm Proteins/metabolism ; Neoplasms/metabolism ; PTEN Phosphohydrolase/metabolism ; Signal Transduction
Chemical Substances	Neoplasm Proteins ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
Language	English
Publishing date	2012-11-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/scisignal.2003685
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Article ; Online: PTEN Protein Phosphatase Activity Is Not Required for Tumour Suppression in the Mouse Prostate.

Wise, Helen M / Harris, Adam / Kriplani, Nisha / Schofield, Adam / Caldwell, Helen / Arends, Mark J / Overton, Ian M / Leslie, Nick R

Biomolecules

2022 Volume 12, Issue 10

Abstract: Loss PTEN function is one of the most common events driving aggressive prostate cancers and biochemically, PTEN is a lipid phosphatase which opposes the activation of the oncogenic PI3K-AKT signalling network. However, PTEN also has additional potential ... ...

Abstract	Loss PTEN function is one of the most common events driving aggressive prostate cancers and biochemically, PTEN is a lipid phosphatase which opposes the activation of the oncogenic PI3K-AKT signalling network. However, PTEN also has additional potential mechanisms of action, including protein phosphatase activity. Using a mutant enzyme, PTEN Y138L, which selectively lacks protein phosphatase activity, we characterised genetically modified mice lacking either the full function of PTEN in the prostate gland or only lacking protein phosphatase activity. The phenotypes of mice carrying a single allele of either wild-type
MeSH term(s)	Animals ; Male ; Mice ; Lipids ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoprotein Phosphatases ; Prostate/metabolism ; Prostatic Neoplasms/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; PTEN Phosphohydrolase/genetics ; PTEN Phosphohydrolase/metabolism
Chemical Substances	Lipids ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; Pten protein, mouse (EC 3.1.3.67)
Language	English
Publishing date	2022-10-19
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12101511
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Article ; Online: P-REX2a driving tumorigenesis by PTEN inhibition.

Leslie, Nick R

Science signaling

2009 Volume 2, Issue 94, Page(s) pe68

Abstract: The phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10) antagonizes phosphoinositide 3-kinase (PI3K) signaling and is one of the most frequently mutated tumor suppressors in human cancers. Its regulation appears complex and is of ... ...

Abstract	The phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10) antagonizes phosphoinositide 3-kinase (PI3K) signaling and is one of the most frequently mutated tumor suppressors in human cancers. Its regulation appears complex and is of great potential clinical importance. The protein P-REX2a (phosphatidylinositol 3,4,5-trisphosphate Rac exchanger 2a), better known as a regulator of the small guanosine triphosphatase Rac, has been identified as a direct regulator of PTEN activity and as a potential oncoprotein. P-REX2a can stimulate cell proliferation by inhibiting PTEN and stimulating downstream PI3K-dependent signaling. This suggests that aberrant control of PTEN by P-REX2a may represent a key tumorigenic mechanism, in agreement with recent studies supporting the pathological relevance of several other proposed PTEN regulators.
MeSH term(s)	Cell Transformation, Neoplastic ; GTPase-Activating Proteins/genetics ; GTPase-Activating Proteins/physiology ; Guanine Nucleotide Exchange Factors ; Humans ; PTEN Phosphohydrolase/antagonists & inhibitors ; Phosphatidylinositol 3-Kinases/metabolism ; Point Mutation ; Signal Transduction
Chemical Substances	GTPase-Activating Proteins ; Guanine Nucleotide Exchange Factors ; PREX2 protein, human ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
Language	English
Publishing date	2009-10-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2417226-1
ISSN	1937-9145 ; 1945-0877
ISSN (online)	1937-9145
ISSN	1945-0877
DOI	10.1126/scisignal.294pe68
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Article ; Online: GSK3 and its interactions with the PI3K/AKT/mTOR signalling network.

Hermida, Miguel A / Dinesh Kumar, J / Leslie, Nick R

Advances in biological regulation

2017 Volume 65, Page(s) 5–15

Abstract: Glycogen Synthase Kinase-3 (GSK3 or GSK-3) is a promiscuous protein kinase and its phosphorylation of its diverse substrates has major influences on many areas of physiology and pathology, including cellular metabolism, lineage commitment and ... ...

Abstract	Glycogen Synthase Kinase-3 (GSK3 or GSK-3) is a promiscuous protein kinase and its phosphorylation of its diverse substrates has major influences on many areas of physiology and pathology, including cellular metabolism, lineage commitment and neuroscience. GSK3 was one of the first identified substrates of the heavily studied oncogenic kinase AKT, phosphorylation by which inhibits GSK3 activity via the formation of an autoinhibitory pseudosubstrate sequence. This has led to investigation of the role of GSK3 inhibition as a key component of the cellular responses to growth factors and insulin, which stimulate the class I PI 3-Kinases and in turn AKT activity and GSK3 phosphorylation. GSK3 has been shown to phosphorylate several upstream and downstream components of the PI3K/AKT/mTOR signalling network, including AKT itself, RICTOR, TSC1 and 2, PTEN and IRS1 and 2, with the potential to apply feedback control within the network. However, it has been clear for some time that functionally distinct, insulated pools of GSK3 exist which are regulated independently, so that for some GSK3 substrates such as β-catenin, phosphorylation by GSK3 is not controlled by input from PI3K and AKT. Instead, as almost all GSK3 substrates require a priming phosphorylated residue to be 4 amino acids C-terminal to the Ser/Thr phosphorylated by GSK3, the predominant form of regulation of the activity of GSK3 often appears to be through control over these priming events, specific to individual substrates. Therefore, a major role of GSK3 can be viewed as an amplifier of the electrostatic effects on protein function which are caused by these priming phosphorylation events. Here we discuss these different aspects to GSK3 regulation and function, and the functions of GSK3 as it integrates with signalling through the PI3K-AKT-mTOR signalling axis.
MeSH term(s)	Animals ; Feedback, Physiological ; Gene Expression Regulation ; Glycogen Synthase Kinase 3/genetics ; Glycogen Synthase Kinase 3/metabolism ; HEK293 Cells ; Humans ; Insulin Receptor Substrate Proteins/genetics ; Insulin Receptor Substrate Proteins/metabolism ; PTEN Phosphohydrolase/genetics ; PTEN Phosphohydrolase/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Rapamycin-Insensitive Companion of mTOR Protein/genetics ; Rapamycin-Insensitive Companion of mTOR Protein/metabolism ; Signal Transduction ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Tuberous Sclerosis Complex 1 Protein ; Tuberous Sclerosis Complex 2 Protein ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
Chemical Substances	IRS1 protein, human ; IRS2 protein, human ; Insulin Receptor Substrate Proteins ; RICTOR protein, human ; Rapamycin-Insensitive Companion of mTOR Protein ; TSC1 protein, human ; Tuberous Sclerosis Complex 1 Protein ; Tuberous Sclerosis Complex 2 Protein ; Tumor Suppressor Proteins ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Glycogen Synthase Kinase 3 (EC 2.7.11.26) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
Language	English
Publishing date	2017-06-27
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2667413-0
ISSN	2212-4934 ; 2212-4926
ISSN (online)	2212-4934
ISSN	2212-4926
DOI	10.1016/j.jbior.2017.06.003
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Article: Acoustotemplating: rapid synthesis of freestanding quasi-2D MOF/graphene oxide heterostructures for supercapacitor applications

Ehrnst, Yemima / Ahmed, Heba / Komljenovic, Robert / Massahud, Emily / Shepelin, Nick A. / Sherrell, Peter C. / Ellis, Amanda V. / Rezk, Amgad R. / Yeo, Leslie Y.

Journal of materials chemistry A. 2022 Mar. 30, v. 10, no. 13

2022

Abstract: Two-dimensional (2D) graphitic materials are often incorporated with metal–organic frameworks (MOFs) to compensate for the poor electrical conductivity of the latter, particularly if they are to be used for electrochemical applications. Nevertheless, the ...

Abstract	Two-dimensional (2D) graphitic materials are often incorporated with metal–organic frameworks (MOFs) to compensate for the poor electrical conductivity of the latter, particularly if they are to be used for electrochemical applications. Nevertheless, the incompatibility between conventional three-dimensional (3D) MOF crystal morphologies with the 2D graphitic sheets often poses a challenge in the fabrication of planar heterostructures, therefore necessitating the addition of polymeric supports and binders. Herein, we report an acoustomicrofluidic method that enables rapid—within milliseconds—synthesis of homogeneous MOF/graphene oxide (GO) planar heterostructures without the need for such additives. In particular, the method harnesses the combination of the intense shear flow and slender-body geometrical confinement imposed by the spreading of a thin liquid film under high frequency electromechanical surface vibrations to drive in situ crystallization and in-plane templating of quasi-2D MOF crystals onto GO sheets simultaneously aligned into stacked layers by the flow. Unlike the 3D morphology of its conventional copper (Cu)-based MOF equivalent (HKUST-1), the unique quasi-2D MOFs that are produced possess large surface-area-to-volume-ratios and dense exposure of Cu sites on their surface that facilitate effective Cu/GO coordination. This ability to template the MOF directly onto the GO sheets allows for the construction of freestanding membranes that are sufficiently robust to withstand reduction of the GO to reduced graphene oxide (rGO) without compromising the integrity of the MOF crystal structure. We show that the synergistic coupling between the conductive rGO layers together with the redox-active surface Cu sites of the quasi-2D MOF enables excellent supercapacitor performance of this hybrid material—up to 292 F g⁻¹ at a current density of 1 A g⁻¹, which is approximately two orders of magnitude larger than its 3D HKUST-1/rGO counterpart.
Keywords	copper ; crystal structure ; crystallization ; electrical conductivity ; electrochemical capacitors ; electrochemistry ; graphene oxide ; liquids
Language	English
Dates of publication	2022-0330
Size	p. 7058-7072.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	2702232-8
ISSN	2050-7496 ; 2050-7488
ISSN (online)	2050-7496
ISSN	2050-7488
DOI	10.1039/d1ta10493d
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Pharmacist and pharmacy intern perceptions of adolescent vaccination administration.

McCauley, Lauren M / Lake, Leslie M / Madison, Nick R / Huntsman, Rachel E / Baker, Chelsea M

Journal of the American Pharmacists Association : JAPhA

2020 Volume 60, Issue 3S, Page(s) S7–S12.e1

Abstract: Objectives: To characterize pharmacists' and pharmacy interns' perceptions of administering adolescent vaccinations. Secondary objectives were to model the association between 1) perceptions and respondent demographic information and 2) pre- and post- ... ...

Abstract	Objectives: To characterize pharmacists' and pharmacy interns' perceptions of administering adolescent vaccinations. Secondary objectives were to model the association between 1) perceptions and respondent demographic information and 2) pre- and post-training survey responses. Design: A 12-item survey, on the basis of the Theory of Self-Perception, was used to collect respondents' perceptions of adolescent vaccination administration retrospectively before and after pharmacist and pharmacy intern completion of Online training. The training reviewed Center for Disease Control and Advisory Committee on Immunization Practice recommendations for vaccination schedules, vaccine administration, managing adverse reactions, finding vaccine-related information, the importance of vaccinating, and dispelling common misconceptions. Setting and participants: Pharmacists and pharmacy interns representing 114 Indiana community pharmacy locations within a national supermarket chain were eligible to complete an Online survey between March and April 2019. Outcome measures: Descriptive statistics were used to characterize pharmacists' and pharmacy interns' perceptions of adolescent vaccination administration. A multivariable regression analysis was used to determine the association between perceptions and respondent demographic information. Differences in perceptions before and after the training module were evaluated using paired t tests. Results: Of the 293 eligible pharmacists and pharmacy interns, 138 (47.1%) completed the survey and 124 (42.3%) responses were included for analysis. Pharmacists and pharmacy interns had positive perceptions of adolescent vaccination administration. There was a negative relationship between the number of years that a pharmacist had been in practice and their baseline perceptions of adolescent vaccination administration (P = 0.02). There was a statistically significant increase in perceptions following completion of the training module (P < 0.001). Conclusion: Pharmacists and pharmacy interns, specifically those who have been in practice for few years, had positive perceptions about adolescent vaccination administration but their perceptions were strengthened with additional training. Further research is needed to determine the relationship between additional training and vaccination rates.
MeSH term(s)	Adolescent ; Community Pharmacy Services ; Humans ; Indiana ; Perception ; Pharmacies ; Pharmacists ; Pharmacy ; Retrospective Studies ; Surveys and Questionnaires ; Vaccination
Language	English
Publishing date	2020-04-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2118585-2
ISSN	1544-3450 ; 1544-3191 ; 1086-5802
ISSN (online)	1544-3450
ISSN	1544-3191 ; 1086-5802
DOI	10.1016/j.japh.2020.03.002
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Article ; Online: Butterfly abundance declines over 20 years of systematic monitoring in Ohio, USA.

Tyson Wepprich / Jeffrey R Adrion / Leslie Ries / Jerome Wiedmann / Nick M Haddad

PLoS ONE, Vol 14, Iss 7, p e

2019 Volume 0216270

Abstract: Severe insect declines make headlines, but they are rarely based on systematic monitoring outside of Europe. We estimate the rate of change in total butterfly abundance and the population trends for 81 species using 21 years of systematic monitoring in ... ...

Abstract	Severe insect declines make headlines, but they are rarely based on systematic monitoring outside of Europe. We estimate the rate of change in total butterfly abundance and the population trends for 81 species using 21 years of systematic monitoring in Ohio, USA. Total abundance is declining at 2% per year, resulting in a cumulative 33% reduction in butterfly abundance. Three times as many species have negative population trends compared to positive trends. The rate of total decline and the proportion of species in decline mirror those documented in three comparable long-term European monitoring programs. Multiple environmental changes such as climate change, habitat degradation, and agricultural practices may contribute to these declines in Ohio and shift the makeup of the butterfly community by benefiting some species over others. Our analysis of life-history traits associated with population trends shows an impact of climate change, as species with northern distributions and fewer annual generations declined more rapidly. However, even common and invasive species associated with human-dominated landscapes are declining, suggesting widespread environmental causes for these trends. Declines in common species, although they may not be close to extinction, will have an outsized impact on the ecosystem services provided by insects. These results from the most extensive, systematic insect monitoring program in North America demonstrate an ongoing defaunation in butterflies that on an annual scale might be imperceptible, but cumulatively has reduced butterfly numbers by a third over 20 years.
Keywords	Medicine ; R ; Science ; Q
Subject code	333
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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