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Article ; Online: Changes in m6A in Steatotic Liver Disease.

Petri, Belinda J / Cave, Matthew C / Klinge, Carolyn M

2023 Volume 14, Issue 8

Abstract: Fatty liver disease is one of the major causes of morbidity and mortality worldwide. Fatty liver includes non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), now replaced by a consensus group as metabolic dysfunction- ... ...

Abstract	Fatty liver disease is one of the major causes of morbidity and mortality worldwide. Fatty liver includes non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), now replaced by a consensus group as metabolic dysfunction-associated steatotic liver disease (MASLD). While excess nutrition and obesity are major contributors to fatty liver, the underlying mechanisms remain largely unknown and therapeutic interventions are limited. Reversible chemical modifications in RNA are newly recognized critical regulators controlling post-transcriptional gene expression. Among these modifications, N6-methyladenosine (m6A) is the most abundant and regulates transcript abundance in fatty liver disease. Modulation of m6A by readers, writers, and erasers (RWE) impacts mRNA processing, translation, nuclear export, localization, and degradation. While many studies focus on m6A RWE expression in human liver pathologies, limitations of technology and bioinformatic methods to detect m6A present challenges in understanding the epitranscriptomic mechanisms driving fatty liver disease progression. In this review, we summarize the RWE of m6A and current methods of detecting m6A in specific genes associated with fatty liver disease.
MeSH term(s)	Humans ; Non-alcoholic Fatty Liver Disease/genetics ; Adenosine/genetics ; Computational Biology ; Nutritional Status
Chemical Substances	Adenosine (K72T3FS567)
Language	English
Publishing date	2023-08-19
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14081653
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Reduction of Aversive Learning Rates in Pavlovian Conditioning by Angiotensin II Antagonist Losartan: A Randomized Controlled Trial.

Zika, Ondrej / Appel, Judith / Klinge, Corinna / Shkreli, Lorika / Browning, Michael / Wiech, Katja / Reinecke, Andrea

Biological psychiatry

2024

Abstract: Background: Angiotensin receptor blockade has been linked to aspects of aversive learning and memory formation and to the prevention of posttraumatic stress disorder symptom development.: Methods: We investigated the influence of the angiotensin ... ...

Abstract	Background: Angiotensin receptor blockade has been linked to aspects of aversive learning and memory formation and to the prevention of posttraumatic stress disorder symptom development. Methods: We investigated the influence of the angiotensin receptor blocker losartan on aversive Pavlovian conditioning using a probabilistic learning paradigm. In a double-blind, randomized, placebo-controlled design, we tested 45 (18 female) healthy volunteers during a baseline session, after application of losartan or placebo (drug session), and during a follow-up session. During each session, participants engaged in a task in which they had to predict the probability of an electrical stimulation on every trial while the true shock contingencies switched repeatedly between phases of high and low shock threat. Computational reinforcement learning models were used to investigate learning dynamics. Results: Acute administration of losartan significantly reduced participants' adjustment during both low-to-high and high-to-low threat changes. This was driven by reduced aversive learning rates in the losartan group during the drug session compared with baseline. The 50-mg drug dose did not induce reduction of blood pressure or change in reaction times, ruling out a general reduction in attention and engagement. Decreased adjustment of aversive expectations was maintained at a follow-up session 24 hours later. Conclusions: This study shows that losartan acutely reduces Pavlovian learning in aversive environments, thereby highlighting a potential role of the renin-angiotensin system in anxiety development.
Language	English
Publishing date	2024-02-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2024.01.020
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Article ; Online: No signs of long-term greening trend in Western Mongolian Grasslands

Hauck, Markus / Klinge, Michael / Erasmi, Stefan / Dulamsuren, Choimaa

2023

Abstract: Trends for increased vegetation greenness based on satellite-derived data have been repeatedly published for the temperate grassland biome (including forest steppes) of eastern Inner Asia since 1982. Although this greening trend has been attenuated or ... ...

Abstract	Trends for increased vegetation greenness based on satellite-derived data have been repeatedly published for the temperate grassland biome (including forest steppes) of eastern Inner Asia since 1982. Although this greening trend has been attenuated or partially reversed by drought in the early twenty-first century, linear increases in the Normalized Difference Vegetation Index (NDVI) or other parameters of vegetation greenness are nevertheless evident when the period since 1982 is regarded. However, the question arises whether these trends are part of a long-term trend driven by climate change, as simultaneously forests in the region show widespread drought-induced growth reductions and mortality outbreaks. Therefore, we hypothesized that the post-1982 greening trend was neither part of a long-term trend nor unprecedented. To test this hypothesis, we analyzed monthly maximum NDVI data from AVHRR time series and correlated these data with standardized tree-ring data of Larix sibirica from two regions of western Mongolia. We used linear regression to model the NDVI from tree-ring anomalies and to reconstruct the NDVI since 1940. These reconstructions show that the availability of satellite-based NDVI data coincidentally began during a dry period of low vegetation greenness in the early 1980s and was followed by a wet phase in the 1990s, producing the linear greening trend. No positive long-term trend in the reconstructed NDVI was observed from 1940 to 2010. This result rules out a recent climate change-driven greening trend for the grasslands and forest steppes of western Mongolia and calls into question its existence for all of eastern Inner Asia.
Keywords	article ; Text ; ddc:570 ; climate change ; NDVI ; productivity ; remote sensing ; Siberian larch (Larix sibirica) ; steppe ; tree-ring analysis
Subject code	333
Language	English
Publisher	Springer
Publishing country	de
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Author Correction: HNRNPA2/B1 is upregulated in endocrine-resistant LCC9 breast cancer cells and alters the miRNA transcriptome when overexpressed in MCF-7 cells.

Klinge, Carolyn M / Piell, Kellianne M / Tooley, Christine Schaner / Rouchka, Eric C

Scientific reports

2021 Volume 11, Issue 1, Page(s) 9235

Language	English
Publishing date	2021-04-23
Publishing country	England
Document type	Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-87869-6
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Article ; Online: Does smoking cessation affect postoperative healing following oral surgery among smokers? - a systematic review.

Olsson, Magnus / Nordendahl, Eva / Klinge, Björn / Ekbom, Anders / Edlund, Christoffer / Fored, Michael / Sundström, Johan / Naimi-Akbar, Aron

BMC oral health

2024 Volume 24, Issue 1, Page(s) 242

Abstract: Background: It is well documented that smokers suffer increased risk of postoperative complications after medical surgery, for example delayed healing and increased risk of infection. It is also known that preoperative smoking cessation can reduce the ... ...

Abstract	Background: It is well documented that smokers suffer increased risk of postoperative complications after medical surgery, for example delayed healing and increased risk of infection. It is also known that preoperative smoking cessation can reduce the risk of these complications. Because of this there are guidelines regarding preoperative smoking cessation in non-oral medical surgery. There are however no specific guidelines regarding oral surgical procedures, such as surgical extractions, dentoalveolar surgery, periodontal surgery, or dental implantation. Nevertheless, it is common that dentists and oral surgeons recommend smoking cessation pre to oral surgical procedures. The aim with this systematic review was to see if there are any evidence in the literature, supporting preoperative smoking cessation in oral surgical procedures. Methods: A systematic search of the electronic databases PubMed, Scopus, Web of Science, and Cochrane was conducted to identify studies addressing the effect of preoperative smoking cessation in oral surgical procedures. Included publications were subjected to preidentified inclusion criterion. Six examiners performed the eligibility and quality assessment of relevant studies. Risk of bias was assessed using ROBINS-I and RoB 2. Certainty assessment was carried out using GRADE. Results: The initial search resulted in 2255 records, and after removal of 148 duplicates, 16 articles met an acceptable level of relevance. These were read in full text, whereof 12 articles were excluded, due to different intervention, outcome, or study design than stated in the review protocol. One study remained with moderate risk of bias and three were excluded due to high risk of bias. Conclusion: This systematic review could not determine the effect of smoking cessation pre to oral surgical procedures, in smokers. This indicates lack of knowledge in the effects of smoking cessation. We also conclude a lack of knowledge in how to design smoking cessation in the most effective way.
MeSH term(s)	Humans ; Smoking Cessation ; Smoking/adverse effects ; Smokers ; Postoperative Complications ; Oral Surgical Procedures
Language	English
Publishing date	2024-02-15
Publishing country	England
Document type	Systematic Review ; Journal Article
ZDB-ID	2091511-1
ISSN	1472-6831 ; 1472-6831
ISSN (online)	1472-6831
ISSN	1472-6831
DOI	10.1186/s12903-024-03989-1
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Article ; Online: Chronic Aroclor 1260 exposure alters the mouse liver proteome, selenoproteins, and metals in steatotic liver disease.

Piell, Kellianne M / Petri, Belinda J / Xu, Jason / Cai, Lu / Rai, Shesh N / Li, Ming / Wilkey, Daniel W / Merchant, Michael L / Cave, Matthew C / Klinge, Carolyn M

Environmental toxicology and pharmacology

2024 Volume 107, Page(s) 104430

Abstract: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to increase due in part to the obesity epidemic and to environmental exposures to metabolism disrupting chemicals. A single gavage exposure of male mice to ... ...

Abstract	The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) continues to increase due in part to the obesity epidemic and to environmental exposures to metabolism disrupting chemicals. A single gavage exposure of male mice to Aroclor 1260 (Ar1260), an environmentally relevant mixture of non-dioxin-like polychlorinated biphenyls (PCBs), resulted in steatohepatitis and altered RNA modifications in selenocysteine tRNA 34 weeks post-exposure. Unbiased approaches identified the liver proteome, selenoproteins, and levels of 25 metals. Ar1260 altered the abundance of 128 proteins. Enrichment analysis of the liver Ar1260 proteome included glutathione metabolism and translation of selenoproteins. Hepatic glutathione peroxidase 4 (GPX4) and Selenoprotein O (SELENOO) were increased and Selenoprotein F (SELENOF), Selenoprotein S (SELENOS), Selenium binding protein 2 (SELENBP2) were decreased with Ar1260 exposure. Increased copper, selenium (Se), and zinc and reduced iron levels were detected. These data demonstrate that Ar1260 exposure alters the (seleno)proteome, Se, and metals in MASLD-associated pathways.
MeSH term(s)	Male ; Mice ; Animals ; Proteome/metabolism ; Glutathione Peroxidase/metabolism ; Selenoproteins/genetics ; Selenoproteins/metabolism ; Liver/metabolism ; Selenium ; Fatty Liver ; Aroclors
Chemical Substances	Proteome ; Glutathione Peroxidase (EC 1.11.1.9) ; aroclor 1260 (11096-82-5) ; Selenoproteins ; Selenium (H6241UJ22B) ; Aroclors
Language	English
Publishing date	2024-03-27
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1318302-3
ISSN	1872-7077 ; 1382-6689
ISSN (online)	1872-7077
ISSN	1382-6689
DOI	10.1016/j.etap.2024.104430
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Article ; Online: Modelling the productivity of Siberian larch forests from Landsat NDVI time series in fragmented forest stands of the Mongolian forest-steppe.

Erasmi, Stefan / Klinge, Michael / Dulamsuren, Choimaa / Schneider, Florian / Hauck, Markus

Environmental monitoring and assessment

2021 Volume 193, Issue 4, Page(s) 200

Abstract: The monitoring of the spatial and temporal dynamics of vegetation productivity is important in the context of carbon sequestration by terrestrial ecosystems from the atmosphere. The accessibility of the full archive of medium-resolution earth observation ...

Abstract	The monitoring of the spatial and temporal dynamics of vegetation productivity is important in the context of carbon sequestration by terrestrial ecosystems from the atmosphere. The accessibility of the full archive of medium-resolution earth observation data for multiple decades dramatically improved the potential of remote sensing to support global climate change and terrestrial carbon cycle studies. We investigated a dense time series of multi-sensor Landsat Normalized Difference Vegetation Index (NDVI) data at the southern fringe of the boreal forests in the Mongolian forest-steppe with regard to the ability to capture the annual variability in radial stemwood increment and thus forest productivity. Forest productivity was assessed from dendrochronological series of Siberian larch (Larix sibirica) from 15 plots in forest patches of different ages and stand sizes. The results revealed a strong correlation between the maximum growing season NDVI of forest sites and tree ring width over an observation period of 20 years. This relationship was independent of the forest stand size and of the landscape's forest-to-grassland ratio. We conclude from the consistent findings of our case study that the maximum growing season NDVI can be used for retrospective modelling of forest productivity over larger areas. The usefulness of grassland NDVI as a proxy for forest NDVI to monitor forest productivity in semi-arid areas could only partially be confirmed. Spatial and temporal inconsistencies between forest and grassland NDVI are a consequence of different physiological and ecological vegetation properties. Due to coarse spatial resolution of available satellite data, previous studies were not able to account for small-scaled land-cover patches like fragmented forest in the forest-steppe. Landsat satellite-time series were able to separate those effects and thus may contribute to a better understanding of the impact of global climate change on natural ecosystems.
MeSH term(s)	Ecosystem ; Environmental Monitoring ; Forests ; Larix ; Retrospective Studies
Language	English
Publishing date	2021-03-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	782621-7
ISSN	1573-2959 ; 0167-6369
ISSN (online)	1573-2959
ISSN	0167-6369
DOI	10.1007/s10661-021-08996-1
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Article ; Online: Changes in m6A in Steatotic Liver Disease

Petri, Belinda J. / Cave, Matthew C. / Klinge, Carolyn M.

Genes (Basel). 2023 Aug. 19, v. 14, no. 8

2023

Abstract	Fatty liver disease is one of the major causes of morbidity and mortality worldwide. Fatty liver includes non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), now replaced by a consensus group as metabolic dysfunction-associated steatotic liver disease (MASLD). While excess nutrition and obesity are major contributors to fatty liver, the underlying mechanisms remain largely unknown and therapeutic interventions are limited. Reversible chemical modifications in RNA are newly recognized critical regulators controlling post-transcriptional gene expression. Among these modifications, N6-methyladenosine (m6A) is the most abundant and regulates transcript abundance in fatty liver disease. Modulation of m6A by readers, writers, and erasers (RWE) impacts mRNA processing, translation, nuclear export, localization, and degradation. While many studies focus on m6A RWE expression in human liver pathologies, limitations of technology and bioinformatic methods to detect m6A present challenges in understanding the epitranscriptomic mechanisms driving fatty liver disease progression. In this review, we summarize the RWE of m6A and current methods of detecting m6A in specific genes associated with fatty liver disease.
Keywords	RNA ; bioinformatics ; disease progression ; fatty liver ; gene expression ; humans ; liver ; mortality ; nutrition ; obesity ; physiological transport ; therapeutics
Language	English
Dates of publication	2023-0819
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes14081653
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Polychlorinated biphenyls alter hepatic m6A mRNA methylation in a mouse model of environmental liver disease.

Petri, Belinda J / Piell, Kellianne M / Wahlang, Banrida / Head, Kimberly Z / Andreeva, Kalina / Rouchka, Eric C / Cave, Matthew C / Klinge, Carolyn M

Environmental research

2022 Volume 216, Issue Pt 3, Page(s) 114686

Abstract: Exposure to polychlorinated biphenyls (PCBs) has been associated with liver injury in human cohorts and with nonalcoholic steatohepatitis (NASH) in mice fed a high fat diet (HFD). N (6)-methyladenosine (m6A) modification of mRNA regulates transcript fate, ...

Abstract	Exposure to polychlorinated biphenyls (PCBs) has been associated with liver injury in human cohorts and with nonalcoholic steatohepatitis (NASH) in mice fed a high fat diet (HFD). N (6)-methyladenosine (m6A) modification of mRNA regulates transcript fate, but the contribution of m6A modification on the regulation of transcripts in PCB-induced steatosis and fibrosis is unknown. This study tested the hypothesis that PCB and HFD exposure alters the levels of m6A modification in transcripts that play a role in NASH in vivo. Male C57Bl6/J mice were fed a HFD (12 wks) and administered a single oral dose of Aroclor1260, PCB126, or Aroclor1260 + PCB126. Genome-wide identification of m6A peaks was accomplished by m6A mRNA immunoprecipitation sequencing (m6A-RIP) and the mRNA transcriptome identified by RNA-seq. Exposure of HFD-fed mice to Aroclor1260 decreased the number of m6A peaks and m6A-containing genes relative to PCB vehicle control whereas PCB126 or the combination of Aroclor1260 + PCB126 increased m6A modification frequency. ∼41% of genes had one m6A peak and ∼49% had 2-4 m6A peaks. 117 m6A peaks were common in the four experimental groups. The Aroclor1260 + PCB126 exposure group showed the highest number (52) of m6A-peaks. qRT-PCR confirmed enrichment of m6A-containing fragments of the Apob transcript with PCB exposure. A1cf transcript abundance, m6A peak count, and protein abundance was increased with Aroclor1260 + PCB126 co-exposure. Irrespective of the PCB type, all PCB groups exhibited enriched pathways related to lipid/lipoprotein metabolism and inflammation through the m6A modification. Integrated analysis of m6A-RIP-seq and mRNA-seq identified 242 differentially expressed genes (DEGs) with increased or reduced number of m6A peaks. These data show that PCB exposure in HFD-fed mice alters the m6A landscape offering an additional layer of regulation of gene expression affecting a subset of gene responses in NASH.
MeSH term(s)	Male ; Mice ; Humans ; Animals ; Polychlorinated Biphenyls/toxicity ; Polychlorinated Biphenyls/metabolism ; Non-alcoholic Fatty Liver Disease/chemically induced ; Non-alcoholic Fatty Liver Disease/genetics ; Methylation ; Liver/metabolism ; Mice, Inbred C57BL ; Disease Models, Animal ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
Chemical Substances	3,4,5,3',4'-pentachlorobiphenyl (TSH69IA9XF) ; Polychlorinated Biphenyls (DFC2HB4I0K) ; RNA, Messenger
Language	English
Publishing date	2022-10-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2022.114686
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Article: Coronary Microvascular Dysfunction in Acute Cholestasis-Induced Liver Injury.

Billig, Sebastian / Hein, Marc / Kirchner, Celine / Schumacher, David / Habigt, Moriz Aljoscha / Mechelinck, Mare / Fuchs, Dieter / Klinge, Uwe / Theißen, Alexander / Beckers, Christian / Bleilevens, Christian / Kramann, Rafael / Uhlig, Moritz

Biomedicines

2024 Volume 12, Issue 4

Abstract: Background: Previous studies have shown cardiac abnormalities in acute liver injury, suggesting a potential role in the associated high mortality.: Methods: We designed an experimental study exploring the short-term effects of acute cholestasis- ... ...

Abstract	Background: Previous studies have shown cardiac abnormalities in acute liver injury, suggesting a potential role in the associated high mortality. Methods: We designed an experimental study exploring the short-term effects of acute cholestasis-induced liver injury on cardiac function and structure in a rodent bile duct ligation (BDL) model to elucidate the potential interplay. Thirty-seven male Results: BDL animals exhibited acute liver injury with elevated transaminases, bilirubin, and total circulating bile acids (TBA) 5 days after BDL (TBA control: 0.81 ± 2.54 µmol/L vs. BDL: 127.52 ± 57.03 µmol/L; Conclusions: In summary, acute cholestasis-induced liver injury can lead to impaired cardiac function mediated by coronary microvascular dysfunction, suggesting that major adverse cardiac events may contribute to the mortality of acute liver failure. This may be due to endothelial dysfunction and direct bile acid signaling.
Language	English
Publishing date	2024-04-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines12040876
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