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Article ; Online: Impact of age and apolipoprotein E ε4 status on regional white matter hyperintensity volume and cognition in healthy aging.

Van Etten, Emily J / Bharadwaj, Pradyumna K / Grilli, Matthew D / Raichlen, David A / Hishaw, Georg A / Huentelman, Matthew J / Trouard, Theodore P / Alexander, Gene E

Journal of the International Neuropsychological Society : JINS

2024 , Page(s) 1–11

Abstract: Objective: White matter hyperintensity (WMH) volume is a neuroimaging marker of lesion load related to small vessel disease that has been associated with cognitive aging and Alzheimer's disease (AD) risk.: Method: The present study sought to examine ... ...

Abstract	Objective: White matter hyperintensity (WMH) volume is a neuroimaging marker of lesion load related to small vessel disease that has been associated with cognitive aging and Alzheimer's disease (AD) risk. Method: The present study sought to examine whether regional WMH volume mediates the relationship between APOE ε4 status, a strong genetic risk factor for AD, and cognition and if this association is moderated by age group differences within a sample of 187 healthy older adults (APOE ε4 status [carrier/non-carrier] = 56/131). Results: After we controlled for sex, education, and vascular risk factors, ANCOVA analyses revealed significant age group by APOE ε4 status interactions for right parietal and left temporal WMH volumes. Within the young-old group (50-69 years), ε4 carriers had greater right parietal and left temporal WMH volumes than non-carriers. However, in the old-old group (70-89 years), right parietal and left temporal WMH volumes were comparable across APOE ε4 groups. Further, within ε4 non-carriers, old-old adults had greater right parietal and left temporal WMH volumes than young-old adults, but there were no significant differences across age groups in ε4 carriers. Follow-up moderated mediation analyses revealed that, in the young-old, but not the old-old group, there were significant indirect effects of ε4 status on memory and executive functions through left temporal WMH volume. Conclusions: These findings suggest that, among healthy young-old adults, increased left temporal WMH volume, in the context of the ε4 allele, may represent an early marker of cognitive aging with the potential to lead to greater risk for AD.
Language	English
Publishing date	2024-03-22
Publishing country	England
Document type	Journal Article
ZDB-ID	1230632-0
ISSN	1469-7661 ; 1355-6177
ISSN (online)	1469-7661
ISSN	1355-6177
DOI	10.1017/S1355617724000122
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Article ; Online: Determining the impact of flavored e-liquids on aldehyde production during Vaping.

Gillman, I Gene / Pennington, Alexander S C / Humphries, Kathy E / Oldham, Michael J

Regulatory toxicology and pharmacology : RTP

2020 Volume 112, Page(s) 104588

Abstract: 1,2-Propylene glycol and glycerin, principal components of e-liquids, can thermally degrade to form ... the flavors in e-liquids were suggested to be the major source of these aldehydes. We used the same 10 ENDS ... devices to test 5 e-liquid formulations (four flavored & one corresponding non-flavored) and measured ...

Abstract	1,2-Propylene glycol and glycerin, principal components of e-liquids, can thermally degrade to form acetaldehyde, acrolein, and formaldehyde when heated in electronic nicotine delivery systems (ENDS). Recently the flavors in e-liquids were suggested to be the major source of these aldehydes. We used the same 10 ENDS devices to test 5 e-liquid formulations (four flavored & one corresponding non-flavored) and measured device mass loss and levels of acetaldehyde, acrolein, and formaldehyde (30 replicate measurements per formulation). Despite finding reasonable variability in measurements of device mass loss, two out of 10 ENDS devices tested produced outlier values for aerosol levels acetaldehyde, acrolein, and formaldehyde. After removing these devices from further analysis, acceptable variability (≤20% RSD) in aerosol levels of acetaldehyde, and formaldehyde were found. The flavored formulations tested resulted in a consistent and selective increase of 150%-200% in acetaldehyde, no increase or decrease in acrolein and depending on the flavor formulation, an increase, a decrease or no change in formaldehyde levels. Comparison of our results to the literature illustrates the need for development of a standardized ENDS testing protocol. Our results further support that device variability must be fully characterized and considered before assessing the impact of e-liquid formulations.
MeSH term(s)	Aldehydes/metabolism ; Flavoring Agents/metabolism ; Humans ; Vaping/metabolism
Chemical Substances	Aldehydes ; Flavoring Agents
Language	English
Publishing date	2020-01-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	604672-1
ISSN	1096-0295 ; 0273-2300
ISSN (online)	1096-0295
ISSN	0273-2300
DOI	10.1016/j.yrtph.2020.104588
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Article ; Online: Ubiquitous mRNA decay fragments in E. coli redefine the functional transcriptome.

Herzel, Lydia / Stanley, Julian A / Yao, Chun-Chen / Li, Gene-Wei

Nucleic acids research

2022 Volume 50, Issue 9, Page(s) 5029–5046

Abstract: Bacterial mRNAs have short life cycles, in which transcription is rapidly followed by translation and degradation within seconds to minutes. The resulting diversity of mRNA molecules across different life-cycle stages impacts their functionality but has ... ...

Abstract	Bacterial mRNAs have short life cycles, in which transcription is rapidly followed by translation and degradation within seconds to minutes. The resulting diversity of mRNA molecules across different life-cycle stages impacts their functionality but has remained unresolved. Here we quantitatively map the 3' status of cellular RNAs in Escherichia coli during steady-state growth and report a large fraction of molecules (median>60%) that are fragments of canonical full-length mRNAs. The majority of RNA fragments are decay intermediates, whereas nascent RNAs contribute to a smaller fraction. Despite the prevalence of decay intermediates in total cellular RNA, these intermediates are underrepresented in the pool of ribosome-associated transcripts and can thus distort quantifications and differential expression analyses for the abundance of full-length, functional mRNAs. The large heterogeneity within mRNA molecules in vivo highlights the importance in discerning functional transcripts and provides a lens for studying the dynamic life cycle of mRNAs.
MeSH term(s)	Escherichia coli/genetics ; Escherichia coli/metabolism ; RNA Stability ; RNA, Bacterial/metabolism ; RNA, Messenger/metabolism ; Ribosomes/genetics ; Ribosomes/metabolism ; Transcriptome
Chemical Substances	RNA, Bacterial ; RNA, Messenger
Language	English
Publishing date	2022-05-07
Publishing country	England
Document type	Journal Article
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkac295
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Article ; Online: Influence of regional white matter hyperintensity volume and apolipoprotein E ε4 status on hippocampal volume in healthy older adults.

Van Etten, Emily J / Bharadwaj, Pradyumna K / Hishaw, Georg A / Huentelman, Matthew J / Trouard, Theodore P / Grilli, Matthew D / Alexander, Gene E

Hippocampus

2021 Volume 31, Issue 5, Page(s) 469–480

Abstract: ... may differentially affect the hippocampus in healthy aging. Additionally, apolipoprotein E (APOE) ε4 carriers may be ...

Abstract	While total white matter hyperintensity (WMH) volume on magnetic resonance imaging (MRI) has been associated with hippocampal atrophy, less is known about how the regional distribution of WMH volume may differentially affect the hippocampus in healthy aging. Additionally, apolipoprotein E (APOE) ε4 carriers may be at an increased risk for greater WMH volumes and hippocampal atrophy in aging. The present study sought to investigate whether regional WMH volume mediates the relationship between age and hippocampal volume and if this association is moderated by APOE ε4 status in a group of 190 cognitively healthy adults (APOE ε4 status [carrier/non-carrier] = 59/131), ages 50-89. Analyses revealed that temporal lobe WMH volume significantly mediated the relationship between age and average bilateral hippocampal volume, and this effect was moderated by APOE ε4 status (-0.020 (SE = 0.009), 95% CI, [-0.039, -0.003]). APOE ε4 carriers, but not non-carriers, showed negative indirect effects of age on hippocampal volume through temporal lobe WMH volume (APOE ε4 carriers: -0.016 (SE = 0.007), 95% CI, [-0.030, -0.003]; APOE ε4 non-carriers: .005 (SE = 0.006), 95% CI, [-0.006, 0.017]). These findings remained significant after additionally adjusting for sex, years of education, hypertension status and duration, cholesterol status, diabetes status, Body Mass Index, history of smoking, and the Wechsler Adult Intelligence Scale-IV Full Scale IQ. There were no significant moderated mediation effects for frontal, parietal, and occipital lobe WMH volumes, with or without covariates. Our findings indicate that in cognitively healthy older adults, elevated WMH volume regionally localized to the temporal lobes in APOE ε4 carriers is associated with reduced hippocampal volume, suggesting greater vulnerability to brain aging and the risk for Alzheimer's disease.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/pathology ; Apolipoprotein E4/genetics ; Hippocampus/diagnostic imaging ; Hippocampus/pathology ; Humans ; Magnetic Resonance Imaging/methods ; Middle Aged ; White Matter/diagnostic imaging ; White Matter/pathology
Chemical Substances	Apolipoprotein E4
Language	English
Publishing date	2021-02-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1074352-2
ISSN	1098-1063 ; 1050-9631
ISSN (online)	1098-1063
ISSN	1050-9631
DOI	10.1002/hipo.23308
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Zs.A 3227: Show issues

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Article: Determination of chemical constituent yields in e-cigarette aerosol using partial and whole pod collections, a comparative analysis.

Jameson, J Brian / Wang, Jiaming / Bailey, Patrick C / Oldham, Michael J / Smith, Cameron R / Jeong, Lena N / Cook, David K / Bates, Austin L / Ullah, Sifat / Pennington, Alexander S C / Gillman, I Gene

Frontiers in chemistry

2023 Volume 11, Page(s) 1223967

Abstract: Literature reports the chemical constituent yields of electronic nicotine delivery systems (ENDS) aerosol collected using a range of aerosol collection strategies. The number of puffs to deplete an ENDS product varies widely, but collections often ... ...

Abstract	Literature reports the chemical constituent yields of electronic nicotine delivery systems (ENDS) aerosol collected using a range of aerosol collection strategies. The number of puffs to deplete an ENDS product varies widely, but collections often consist of data from the first 50-100 puffs. However, it is not clear whether these discrete puff blocks are representative of constituent yields over the life of a pod. We aimed to assess the effect of differing aerosol collection strategies on reported yields for select chemical constituents in the aerosol of closed pod-based ENDS products. Constituents analyzed were chosen to reflect important classes of compounds from the Final Premarket Tobacco Product Application Guidance. Yields were normalized to total device mass loss (DML). Collection strategies that consisted of partial pod collection were valid for determining yields of constituents whose DML normalized yields were consistent for the duration of pod life. These included primary aerosol constituents, such as propylene glycol, glycerol, and nicotine, and whole pod yields could be determined from initial puff blocks. However, changes were observed in the yields of some metals, some carbonyl compounds, and glycidol over pod life in a chemical constituent and product dependent manner. These results suggest that collection strategies consisting of initial puff block collections require validation per chemical constituent/product and are not appropriate for chemical constituents with variable yields over pod life. Whole pod collection increased sensitivity and accuracy in determining metal, carbonyl, and glycidol yields compared to puff block-based collection methodologies for all products tested.
Language	English
Publishing date	2023-09-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711776-5
ISSN	2296-2646
ISSN	2296-2646
DOI	10.3389/fchem.2023.1223967
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Article ; Online: Reflux conditions induce E-cadherin cleavage and EMT via APE1 redox function in oesophageal adenocarcinoma.

Lu, Heng / Cao, Long Long / Ballout, Farah / Belkhiri, Abbes / Peng, DunFa / Chen, Lei / Chen, Zheng / Soutto, Mohammed / Wang, Timothy C / Que, Jianwen / Giordano, Silvia / Washington, Mary Kay / Chen, Steven / McDonald, Oliver Gene / Zaika, Alexander / El-Rifai, Wael

Gut

2023 Volume 73, Issue 1, Page(s) 47–62

Abstract: ... of the EMT process, such as downregulation of E-cadherin, upregulation of vimentin and activation of ß ... enhancement of cell migration and invasion capabilities. Mechanistically, ABS induced E-cadherin cleavage via ... correlated with E-cadherin expression in human EAC tissues and the squamocolumnar junctions of the L2-IL1ß ...

Abstract	Objective: Chronic gastro-oesophageal reflux disease, where acidic bile salts (ABS) reflux into the oesophagus, is the leading risk factor for oesophageal adenocarcinoma (EAC). We investigated the role of ABS in promoting epithelial-mesenchymal transition (EMT) in EAC. Design: RNA sequencing data and public databases were analysed for the EMT pathway enrichment and patients' relapse-free survival. Cell models, pL2-IL1β transgenic mice, deidentified EAC patients' derived xenografts (PDXs) and tissues were used to investigate EMT in EAC. Results: Analysis of public databases and RNA-sequencing data demonstrated significant enrichment and activation of EMT signalling in EAC. ABS induced multiple characteristics of the EMT process, such as downregulation of E-cadherin, upregulation of vimentin and activation of ß-catenin signalling and EMT-transcription factors. These were associated with morphological changes and enhancement of cell migration and invasion capabilities. Mechanistically, ABS induced E-cadherin cleavage via an MMP14-dependent proteolytic cascade. Apurinic/apyrimidinic endonuclease (APE1), also known as redox factor 1, is an essential multifunctional protein. APE1 silencing, or its redox-specific inhibitor (E3330), downregulated MMP14 and abrogated the ABS-induced EMT. APE1 and MMP14 coexpression levels were inversely correlated with E-cadherin expression in human EAC tissues and the squamocolumnar junctions of the L2-IL1ß transgenic mouse model of EAC. EAC patients with APE1 Conclusion: Reflux conditions promote EMT via APE1 redox-dependent E-cadherin cleavage. APE1-redox function inhibitors can have a therapeutic role in EAC.
MeSH term(s)	Humans ; Animals ; Mice ; Matrix Metalloproteinase 14/metabolism ; Adenocarcinoma/pathology ; Oxidation-Reduction ; Gastroesophageal Reflux ; Epithelial-Mesenchymal Transition ; Cadherins/metabolism ; Cell Line, Tumor
Chemical Substances	E 3330 (136164-66-4) ; Matrix Metalloproteinase 14 (EC 3.4.24.80) ; Cadherins
Language	English
Publishing date	2023-12-07
Publishing country	England
Document type	Journal Article
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2023-329455
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Article: Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations.

Farsalinos, Konstantinos E / Gillman, Gene

Frontiers in physiology

2018 Volume 8, Page(s) 1119

Abstract: ... the studies evaluating carbonyl emissions from e-cigarettes. A total of 32 studies were identified and ... the presence of dry puff conditions. Whenever realistic use conditions were ensured, carbonyl emissions from e ...

Abstract	Carbonyl emissions from tobacco cigarettes represent a substantial health risk contributing to smoking-related morbidity and mortality. As expected, this is an important research topic for tobacco harm reduction products, in an attempt to compare the relative risk of these products compared to tobacco cigarettes. In this study, a systematic review of the literature available on PubMed was performed analyzing the studies evaluating carbonyl emissions from e-cigarettes. A total of 32 studies were identified and presented. We identified a large diversity of methodologies, with substantial discrepancies in puffing patterns, aerosol collection and analytical methods as well as reported units of measurements. Such discrepancies make comparisons difficult, and in some cases the accuracy of the findings cannot be determined. Importantly, control for the generation of dry puffs was not performed in the vast majority of studies, particularly in studies using variable power devices, which could result in testing conditions and reported carbonyl levels that have no clinical relevance or context. Some studies have been replicated, verifying the presence of dry puff conditions. Whenever realistic use conditions were ensured, carbonyl emissions from e-cigarettes were substantially lower than tobacco cigarette smoke, while newer generation (bottom-coil, cotton wick) atomizers appeared to emit minimal levels of carbonyls with questionable clinical significance in terms of health risk. However, extremely high levels of carbonyl emissions were reported in some studies, and all these studies need to be replicated because of potentially important health implications.
Language	English
Publishing date	2018-01-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2017.01119
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Article ; Online: Streamlined Operational Approaches and Use of e-Technologies in Clinical Trials: Beat Acute Myeloid Leukemia Master Trial.

Therapeutic innovation & regulatory science

2021 Volume 55, Issue 5, Page(s) 926–935

Abstract: ... We hypothesized that integrating operational strategies with new electronic technologies (e-technologies ... around the guiding principle of "patients first." The e-technology platforms employed in BAML include: Clinical ... Oversight Platform: a central collaborative tool; e-Protocol/e-Source Upload/Electronic Data Capture ...

Abstract	Advances in genomic technologies and an increased understanding of the molecular pathogenesis of cancer have resulted in development of new effective, mutation-targeted therapies. In turn, these informed the development of Master Trial designs to test these therapies. The Beat Acute Myeloid Leukemia (BAML) Master Trial (Sponsor: The Leukemia & Lymphoma Society) tests several targeted therapies in patients aged ≥ 60 years with AML based on genomic profiling obtained within 7 days of study enrollment. We hypothesized that integrating operational strategies with new electronic technologies (e-technologies) might streamline the conduct and management of this Master Trial. BAML's 5 core operational strategies revolve around the guiding principle of "patients first." The e-technology platforms employed in BAML include: Clinical Oversight Platform: a central collaborative tool; e-Protocol/e-Source Upload/Electronic Data Capture Platform: digitizes the protocol, allows remote data monitoring, and collects/exports data in Study Data Tabulation Model format; and Data Review Platform: ingests data from different sources for clinical response and safety data reviews. The operational approaches, e-technologies and sponsor/contract research organization's (CRO) expertise together allow: the complexity and size of the BAML Master Trial to be better managed; near real-time study data oversight; better collaboration, communication and training; improved data collection, enhanced transmission and accessibility; data integration, review and generation of reports; while maintaining data privacy, and compliance. Initial e-technology challenges were overcome through training, learning, discipline and adjustment. In conclusion, to successfully manage Master Trials, significant time should be spent re-evaluating, improving and developing new operational approaches.Clinical Trial Registration: Clinical Trials.gov Identifier: NCT03013998. https://clinicaltrials.gov/ct2/show/NCT03013998 .
MeSH term(s)	Clinical Trials as Topic ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Technology
Language	English
Publishing date	2021-05-16
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2708397-4
ISSN	2168-4804 ; 2168-4790
ISSN (online)	2168-4804
ISSN	2168-4790
DOI	10.1007/s43441-021-00277-w
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Article ; Online: The influence of an esports-adapted coping effectiveness training (E-CET) on resilience, mental health, and subjective performance among elite league of Legends players: A pilot study.

Poulus, Dylan R / Bennett, Kyle Jm / Swann, Christian / Moyle, Gene M / Polman, Remco Cj

Psychology of sport and exercise

2023 Volume 69, Page(s) 102510

Abstract: Objective: This study aimed to develop, and pilot esports-adapted coping effectiveness training (E ... research design. The effects of E-CET were measured using a within-subjects quasi-experimental design (i.e., pre ... to-post, no control group). To measure the effects of E-CET on specific stressors, a longitudinal diary ...

Abstract	Objective: This study aimed to develop, and pilot esports-adapted coping effectiveness training (E-CET) and measure its influence on coping effectiveness (global and specific), subjective performance, mental health (psychological distress and wellbeing), and resilience. Design: Five elite male League of Legends players competing in the League of Legends Circuit Oceania participated in a mixed methods research design. The effects of E-CET were measured using a within-subjects quasi-experimental design (i.e., pre-to-post, no control group). To measure the effects of E-CET on specific stressors, a longitudinal diary design was used. Method: Players participated in a 2-h session of E-CET and a 45-min follow-up workshop. The 2-h workshop delivered content on two conceptual areas: (1) developing awareness of the stress and coping process; and (2) how to cope with stress. Players completed pre-intervention, post-intervention, and follow-up measures and twice-weekly stress journals. Results: E-CET led to increases in players' perceived coping effectiveness and subjective performance, but there were no changes in psychological distress, psychological wellbeing, and resilience. However, the results indicate some positive signs for future coping interventions with League of Legends players and iterations of E-CET. Conclusion: The E-CET program appears to provide an opportunity to improve performance and mental health for esports players.
MeSH term(s)	Male ; Humans ; Mental Health ; Pilot Projects ; Adaptation, Psychological ; Control Groups ; Hyaluronic Acid
Chemical Substances	Hyaluronic Acid (9004-61-9)
Language	English
Publishing date	2023-08-19
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1878-5476
ISSN (online)	1878-5476
DOI	10.1016/j.psychsport.2023.102510
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Article ; Online: Biemamides A-E, Inhibitors of the TGF-β Pathway That Block the Epithelial to Mesenchymal Transition.

Zhang, Fan / Braun, Doug R / Ananiev, Gene E / Hoffmann, F Michael / Tsai, I-Wei / Rajski, Scott R / Bugni, Tim S

Organic letters

2018 Volume 20, Issue 18, Page(s) 5529–5532

Abstract: ... pyrimidinedione derivatives, biemamides A-E (1-5). The structures were determined by 2D NMR and HRMS experiments ... absolute configurations were established by advanced Marfey's analysis and ECD calculations. Biemamides A-E ...

Abstract	Screening of a marine natural products library for inhibitors of TGF-β revealed five pyrimidinedione derivatives, biemamides A-E (1-5). The structures were determined by 2D NMR and HRMS experiments; absolute configurations were established by advanced Marfey's analysis and ECD calculations. Biemamides A-E specifically inhibited in vitro TGF-β induced epithelial to mesenchymal transition in NMuMG cells. Additionally, using Caenorhabditis elegans, selected biemmamides were found to influence in vivo developmental processes related to body size regulation in a dose-dependent manner.
MeSH term(s)	Animals ; Biological Products/chemistry ; Biological Products/pharmacology ; Caenorhabditis elegans/drug effects ; Caenorhabditis elegans/growth & development ; Caenorhabditis elegans/metabolism ; Cell Line ; Dose-Response Relationship, Drug ; Epithelial-Mesenchymal Transition/drug effects ; Humans ; Pyrimidinones/chemistry ; Pyrimidinones/pharmacology ; Structure-Activity Relationship ; Transforming Growth Factor beta/antagonists & inhibitors ; Transforming Growth Factor beta/metabolism
Chemical Substances	Biological Products ; Pyrimidinones ; Transforming Growth Factor beta
Language	English
Publishing date	2018-08-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1523-7052
ISSN (online)	1523-7052
DOI	10.1021/acs.orglett.8b01871
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