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Article ; Online: Abnormal methylation in the

Hörberg, Johanna / Hallbäck, Björn / Moreau, Kevin / Reymer, Anna

QRB discovery

2022 Volume 3, Page(s) e23

Abstract: Selective DNA binding by transcription factors (TFs) is crucial for the correct regulation of DNA transcription. In healthy cells, promoters of active genes are hypomethylated. A single CpG methylation within a TF response element (RE) may change the ... ...

Abstract	Selective DNA binding by transcription factors (TFs) is crucial for the correct regulation of DNA transcription. In healthy cells, promoters of active genes are hypomethylated. A single CpG methylation within a TF response element (RE) may change the binding preferences of the protein, thus causing the dysregulation of transcription programs. Here, we investigate a molecular mechanism driving the downregulation of the
Language	English
Publishing date	2022-11-28
Publishing country	England
Document type	Journal Article
ISSN	2633-2892
ISSN (online)	2633-2892
DOI	10.1017/qrd.2022.21
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Article ; Online: Macroecological diversification of ants is linked to angiosperm evolution.

Nelsen, Matthew P / Moreau, Corrie S / Kevin Boyce, C / Ree, Richard H

Evolution letters

2023 Volume 7, Issue 2, Page(s) 79–87

Abstract: Ants are abundant, diverse, and occupy nearly all habitats and regions of the world. Previous work has demonstrated that ant diversification coincided with the rise of the angiosperms, and that several plant traits evolved as ants began to expand their ... ...

Abstract	Ants are abundant, diverse, and occupy nearly all habitats and regions of the world. Previous work has demonstrated that ant diversification coincided with the rise of the angiosperms, and that several plant traits evolved as ants began to expand their nesting and foraging habits. In this study, we investigate whether associations with plants enabled niche expansion and are linked to climatic niche evolution in ants. Our analysis of over 1,400 ant species reveals that ancestral expansion from forest floors into the canopy and out into non-forested habitats closely followed evolutionary innovations in angiosperms. Several Paleogene-Neogene ant lineages independently diversified in non-forested habitats on multiple continents, tracking the evolution and expansion of elaiosome-bearing and arid-adapted angiosperms. The evolution of arboreal nesting tracked shifts in angiosperm physiology associated with the onset of everwet tropical rainforests, and climatic optima and rates of climatic niche evolution were linked to nesting location, with arboreally nesting groups having warmer and less seasonal climatic optima, and lower rates of climatic niche evolution. Our work further underscores the varied paths by which niche diversification occurred in ants, and how angiosperms influenced the ecological and evolutionary trajectories of interacting lineages.
Language	English
Publishing date	2023-03-31
Publishing country	England
Document type	Journal Article
ISSN	2056-3744
ISSN (online)	2056-3744
DOI	10.1093/evlett/qrad008
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Article ; Online: Homologous basic helix-loop-helix transcription factors induce distinct deformations of torsionally-stressed DNA: a potential transcription regulation mechanism.

Hörberg, Johanna / Moreau, Kevin / Reymer, Anna

QRB discovery

2022 Volume 3, Page(s) e4

Abstract: Changing torsional restraints on DNA is essential for the regulation of transcription. Torsional stress, introduced by RNA polymerase, can propagate along chromatin facilitating topological transitions and modulating the specific binding of transcription ...

Abstract	Changing torsional restraints on DNA is essential for the regulation of transcription. Torsional stress, introduced by RNA polymerase, can propagate along chromatin facilitating topological transitions and modulating the specific binding of transcription factors (TFs) to DNA. Despite the importance, the mechanistic details on how torsional stress impacts the TFs-DNA complexation remain scarce. Herein, we address the impact of torsional stress on DNA complexation with homologous human basic helix-loop-helix (BHLH) hetero- and homodimers: MycMax, MadMax and MaxMax. The three TF dimers exhibit specificity towards the same DNA consensus sequence, the
Language	English
Publishing date	2022-06-10
Publishing country	England
Document type	Journal Article
ISSN	2633-2892
ISSN (online)	2633-2892
DOI	10.1017/qrd.2022.5
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Article ; Online: Pan-azole-resistant Meyerozyma guilliermondii clonal isolates harbouring a double F126L and L505F mutation in Erg11.

Moreau, Jérémy / Noël, Thierry / Point, Kévin / Tewes, Frédéric / Deroche, Luc / Clarhaut, Jonathan / Fitton-Ouhabi, Valérie / Perraud, Estelle / Marchand, Sandrine / Buyck, Julien M / Brunet, Kévin

Mycoses

2024 Volume 67, Issue 3, Page(s) e13704

Abstract: Background: Meyerozyma guilliermondii is a yeast species responsible for invasive fungal infections. It has high minimum inhibitory concentrations (MICs) to echinocandins, the first-line treatment of candidemia. In this context, azole antifungal agents ... ...

Abstract	Background: Meyerozyma guilliermondii is a yeast species responsible for invasive fungal infections. It has high minimum inhibitory concentrations (MICs) to echinocandins, the first-line treatment of candidemia. In this context, azole antifungal agents are frequently used. However, in recent years, a number of azole-resistant strains have been described. Their mechanisms of resistance are currently poorly studied. Objective: The aim of this study was consequently to understand the mechanisms of azole resistance in several clinical isolates of M. guilliermondii. Methods: Ten isolates of M. guilliermondii and the ATCC 6260 reference strain were studied. MICs of azoles were determined first. Whole genome sequencing of the isolates was then carried out and the mutations identified in ERG11 were expressed in a CTG clade yeast model (C. lusitaniae). RNA expression of ERG11, MDR1 and CDR1 was evaluated by quantitative PCR. A phylogenic analysis was developed and performed on M. guilliermondii isolates. Lastly, in vitro experiments on fitness cost and virulence were carried out. Results: Of the ten isolates tested, three showed pan-azole resistance. A combination of F126L and L505F mutations in Erg11 was highlighted in these three isolates. Interestingly, a combination of these two mutations was necessary to confer azole resistance. An overexpression of the Cdr1 efflux pump was also evidenced in one strain. Moreover, the three pan-azole-resistant isolates were shown to be genetically related and not associated with a fitness cost or a lower virulence, suggesting a possible clonal transmission. Conclusion: In conclusion, this study identified an original combination of ERG11 mutations responsible for pan-azole-resistance in M. guilliermondii. Moreover, we proposed a new MLST analysis for M. guilliermondii that identified possible clonal transmission of pan-azole-resistant strains. Future studies are needed to investigate the distribution of this clone in hospital environment and should lead to the reconsideration of the treatment for this species.
MeSH term(s)	Humans ; Azoles/pharmacology ; Multilocus Sequence Typing ; Drug Resistance, Fungal/genetics ; Antifungal Agents/pharmacology ; Mutation ; Microbial Sensitivity Tests ; Fluconazole/pharmacology ; Saccharomycetales
Chemical Substances	Azoles ; Antifungal Agents ; Fluconazole (8VZV102JFY)
Language	English
Publishing date	2024-03-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	392487-7
ISSN	1439-0507 ; 0933-7407
ISSN (online)	1439-0507
ISSN	0933-7407
DOI	10.1111/myc.13704
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Article ; Online: Industry perspective on the nonclinical safety assessment of heterobifunctional degraders.

Hemkens, Michelle / Stamp, Katie / Loberg, Lise I / Moreau, Kevin / Hart, Tim

Drug discovery today

2023 Volume 28, Issue 8, Page(s) 103643

Abstract: Targeted protein degraders (TPDs), which act through the ubiquitin proteasome system (UPS), are one of the newest small-molecule drug modalities. Since the initiation of the first clinical trial in 2019, investigating the use of ARV-110 in patients with ... ...

Abstract	Targeted protein degraders (TPDs), which act through the ubiquitin proteasome system (UPS), are one of the newest small-molecule drug modalities. Since the initiation of the first clinical trial in 2019, investigating the use of ARV-110 in patients with cancer, the field has rapidly expanded. Recently, some theoretical absorption, distribution, metabolism, and excretion (ADME) and safety challenges have been posed for the modality. Using these theoretical concerns as a framework, the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ Consortium) Protein Degrader Working Group (WG) conducted two surveys to benchmark current preclinical practices for TPDs. Conceptually, the safety assessment of TPDs is the same as for standard small molecules; however, the techniques used, assay conditions/study endpoints, and timing of assessments might need to be modified to address differences in mode of action of the class.
MeSH term(s)	Humans ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis Targeting Chimera
Chemical Substances	Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Proteolysis Targeting Chimera
Language	English
Publishing date	2023-05-26
Publishing country	England
Document type	Journal Article
ZDB-ID	1324988-5
ISSN	1878-5832 ; 1359-6446
ISSN (online)	1878-5832
ISSN	1359-6446
DOI	10.1016/j.drudis.2023.103643
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Zs.A 4725: Show issues

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Article ; Online: Abnormal methylation in the NDUFA13 gene promoter of breast cancer cells breaks the cooperative DNA recognition by transcription factors

Johanna Hörberg / Björn Hallbäck / Kevin Moreau / Anna Reymer

QRB Discovery, Vol

2022 Volume 3

Abstract	Selective DNA binding by transcription factors (TFs) is crucial for the correct regulation of DNA transcription. In healthy cells, promoters of active genes are hypomethylated. A single CpG methylation within a TF response element (RE) may change the binding preferences of the protein, thus causing the dysregulation of transcription programs. Here, we investigate a molecular mechanism driving the downregulation of the NDUFA13 gene, due to hypermethylation, which is associated with multiple cancers. Using bioinformatic analyses of breast cancer cell line MCF7, we identify a hypermethylated region containing the binding sites of two TFs dimers, CEBPB and E2F1-DP1, located 130 b.p. from the gene transcription start site. All-atom extended MD simulations of wild type and methylated DNA alone and in complex with either one or both TFs dimers provide mechanistic insights into the cooperative asymmetric binding order of the two dimers; the CEBPB binding should occur first to facilitate the E2F1-DP1–DNA association. The CpG methylation within the E2F1-DP1 RE and the linker decrease the cooperativity effects and renders the E2F1-DP1 binding site less recognizable by the TF dimer. Taken together, the identified CpG methylation site may contribute to the downregulation of the NDUFA13 gene.
Keywords	Transcription factor-DNA recognition ; cooperative DNA binding ; abnormal DNA methylation ; transcription regulation ; molecular dynamics simulations ; bioinformatic analyses ; Biotechnology ; TP248.13-248.65 ; Biology (General) ; QH301-705.5
Subject code	570 ; 612
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Cambridge University Press
Document type	Article ; Online
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Article ; Online: Reorganization in the macaque interoceptive-allostatic network following anterior cingulate cortex damage.

Charbonneau, Joey A / Bennett, Jeffrey L / Chau, Kevin / Bliss-Moreau, Eliza

Cerebral cortex (New York, N.Y. : 1991)

2022 Volume 33, Issue 8, Page(s) 4334–4349

Abstract: Accumulating evidence indicates that the adult brain is capable of significant structural change following damage-a capacity once thought to be largely limited to developing brains. To date, most existing research on adult plasticity has focused on how ... ...

Abstract	Accumulating evidence indicates that the adult brain is capable of significant structural change following damage-a capacity once thought to be largely limited to developing brains. To date, most existing research on adult plasticity has focused on how exteroceptive sensorimotor networks compensate for damage to preserve function. Interoceptive networks-those that represent and process sensory information about the body's internal state-are now recognized to be critical for a wide range of physiological and psychological functions from basic energy regulation to maintaining a sense of self, but the extent to which these networks remain plastic in adulthood has not been established. In this report, we used detailed histological analyses to pinpoint precise changes to gray matter volume in the interoceptive-allostatic network in adult rhesus monkeys (Macaca mulatta) who received neurotoxic lesions of the anterior cingulate cortex (ACC) and neurologically intact control monkeys. Relative to controls, monkeys with ACC lesions had significant and selective unilateral expansion of the ventral anterior insula and significant relative bilateral expansion of the lateral nucleus of the amygdala. This work demonstrates the capacity for neuroplasticity in the interoceptive-allostatic network which, given that changes included expansion rather than atrophy, is likely to represent an adaptive response following damage.
MeSH term(s)	Animals ; Gyrus Cinguli/physiology ; Cerebral Cortex/physiology ; Brain/physiology ; Brain Mapping ; Macaca mulatta
Language	English
Publishing date	2022-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhac346
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Zs.A 3235: Show issues

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Article ; Online: Deciphering the Dynamic Landscape of Transcription-Associated mRNP Quality Control Components Over the Whole Yeast Genome.

Moreau, Kévin / Le Dantec, Aurélia / Rahmouni, A Rachid

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

2020 Volume 2209, Page(s) 251–265

Abstract: In eukaryotic cells, aberrant mRNPs with processing and packaging defects are targeted co-transcriptionally by a surveillance system that triggers their nuclear retention and ultimately the degradation of their mRNA component by the 3'-5' activity of the ...

Abstract	In eukaryotic cells, aberrant mRNPs with processing and packaging defects are targeted co-transcriptionally by a surveillance system that triggers their nuclear retention and ultimately the degradation of their mRNA component by the 3'-5' activity of the exosome-associated exonuclease Rrp6. This mRNP quality control process is stimulated by the NNS complex (Nrd1-Nab3-Sen1), which otherwise mediates termination, processing, and decay of ncRNAs. The process involves also the exosome co-activator TRAMP complex (Trf4-Air2-Mtr4). Here, we describe a genome-wide approach to visualize the dynamic movement and coordination of these quality control components over the yeast chromosomes upon perturbation of mRNP biogenesis. The method provides valuable information on how the surveillance system is precisely coordinated both physically and functionally with the transcription machinery to detect the faulty events during perturbation of mRNP biogenesis. The overview shows also that the gathering of the quality control components over affected mRNA genes takes place at the expense of their commitment to be recruited at ncRNA genomic features, provoking termination and processing defects of ncRNAs.
MeSH term(s)	Gene Expression Regulation, Fungal ; High-Throughput Nucleotide Sequencing/methods ; RNA, Fungal/genetics ; RNA, Messenger/genetics ; RNA, Untranslated/genetics ; RNA-Binding Proteins/chemistry ; Ribonucleoproteins/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/chemistry ; Transcription, Genetic
Chemical Substances	RNA, Fungal ; RNA, Messenger ; RNA, Untranslated ; RNA-Binding Proteins ; Ribonucleoproteins ; Saccharomyces cerevisiae Proteins ; messenger ribonucleoprotein
Language	English
Publishing date	2020-11-17
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0935-4_16
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: La biogenèse des autophagosomes perd de son mystère.

Moreau, Kévin

Medecine sciences : M/S

2011 Volume 27, Issue 12, Page(s) 1075–1077

Title translation	Unraveling the secrets of autophagosome formation.
MeSH term(s)	Aging/metabolism ; Aging/physiology ; Autophagy/physiology ; Disease/etiology ; Homeostasis/genetics ; Homeostasis/physiology ; Humans ; Immunity, Cellular/physiology ; Models, Biological ; Phagosomes/metabolism ; Phagosomes/physiology ; Transport Vesicles/physiology ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/physiology
Chemical Substances	Vesicular Transport Proteins
Language	French
Publishing date	2011-12
Publishing country	France
Document type	News
ZDB-ID	632733-3
ISSN	1958-5381 ; 0767-0974
ISSN (online)	1958-5381
ISSN	0767-0974
DOI	10.1051/medsci/20112712013
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Zs.B 2872: Show issues

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Article: Spironolactone as a Potential New Treatment to Prevent Arrhythmias in Arrhythmogenic Cardiomyopathy Cell Model.

Reisqs, Jean-Baptiste / Moreau, Adrien / Sleiman, Yvonne / Charrabi, Azzouz / Delinière, Antoine / Bessière, Francis / Gardey, Kevin / Richard, Sylvain / Chevalier, Philippe

Journal of personalized medicine

2023 Volume 13, Issue 2

Abstract: Arrhythmogenic cardiomyopathy (ACM) is a rare genetic disease associated with ventricular arrhythmias in patients. The occurrence of these arrhythmias is due to direct electrophysiological remodeling of the cardiomyocytes, namely a reduction in the ... ...

Abstract	Arrhythmogenic cardiomyopathy (ACM) is a rare genetic disease associated with ventricular arrhythmias in patients. The occurrence of these arrhythmias is due to direct electrophysiological remodeling of the cardiomyocytes, namely a reduction in the action potential duration (APD) and a disturbance of Ca
Language	English
Publishing date	2023-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662248-8
ISSN	2075-4426
ISSN	2075-4426
DOI	10.3390/jpm13020335
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