@article{Ormancey2023b,

title = {Complementary peptides represent a credible alternative to agrochemicals by activating translation of targeted proteins},

author = {M Ormancey and B Guillotin and R Merret and L Camborde and C Duboe and B Fabre and C Pouzet and F Impens and D Van Haver and M C Carpentier and H S Clemente and M Aguilar and D Lauressergues and L B Scharff and C Pichereaux and O Burlet-Schiltz and C Bousquet-Antonelli and K Gevaert and P Thuleau and S Plaza and J P Combier},

doi = {10.1038/s41467-023-35951-0},

issn = {2041-1723 (Electronic) 2041-1723 (Linking)},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Nat Commun},

volume = {14},

issue = {1},

pages = {254},

abstract = {The current agriculture main challenge is to maintain food production while facing multiple threats such as increasing world population, temperature increase, lack of agrochemicals due to health issues and uprising of weeds resistant to herbicides. Developing novel, alternative, and safe methods is hence of paramount importance. Here, we show that complementary peptides (cPEPs) from any gene can be designed to target specifically plant coding genes. External application of synthetic peptides increases the abundance of the targeted protein, leading to related phenotypes. Moreover, we provide evidence that cPEPs can be powerful tools in agronomy to improve plant traits, such as growth, resistance to pathogen or heat stress, without the needs of genetic approaches. Finally, by combining their activity they can also be used to reduce weed growth.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Binda2022b,

title = {SMA-linked SMN mutants prevent phase separation properties and SMN interactions with FMRP family members},

author = {Olivier Binda and Franceline Juillard and Julia Novion Ducassou and Constance Kleijwegt and Geneviève Paris and Andréanne Didillon and Faouzi Baklouti and Armelle Corpet and Yohann Couté and Jocelyn Côté and Patrick Lomonte},

doi = {10.26508/lsa.202201429},

issn = {2575-1077},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Life Science Alliance},

volume = {6},

issue = {1},

pages = {e202201429},

abstract = {Although recent advances in gene therapy provide hope for spinal muscular atrophy (SMA) patients, the pathology remains the leading genetic cause of infant mortality. SMA is a monogenic pathology that originates from the loss of the SMN1 gene in most cases or mutations in rare cases. Interestingly, several SMN1 mutations occur within the TUDOR methylarginine reader domain of SMN. We hypothesized that in SMN1 mutant cases, SMA may emerge from aberrant protein-protein interactions between SMN and key neuronal factors. Using a BioID proteomic approach, we have identified and validated a number of SMN-interacting proteins, including fragile X mental retardation protein (FMRP) family members (FMRFM). Importantly, SMA-linked SMNTUDOR mutant forms (SMNST) failed to interact with FMRFM In agreement with the recent work, we define biochemically that SMN forms droplets in vitro and these droplets are stabilized by RNA, suggesting that SMN could be involved in the formation of membraneless organelles, such as Cajal nuclear bodies. Finally, we found that SMN and FMRP co-fractionate with polysomes, in an RNA-dependent manner, suggesting a potential role in localized translation in motor neurons.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ielasi2022b,

title = {Human histone pre-mRNA assembles histone or canonical mRNA-processing complexes by overlapping 3'-end sequence elements},

author = {Francesco S Ielasi and Sara Ternifi and Emeline Fontaine and Domenico Iuso and Yohann Couté and Andrés Palencia},

doi = {10.1093/nar/gkac878},

issn = {1362-4962},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nucleic Acids Research},

volume = {50},

issue = {21},

pages = {12425-12443},

abstract = {Human pre-mRNA processing relies on multi-subunit macromolecular complexes, which recognize specific RNA sequence elements essential for assembly and activity. Canonical pre-mRNA processing proceeds via the recognition of a polyadenylation signal (PAS) and a downstream sequence element (DSE), and produces polyadenylated mature mRNAs, while replication-dependent (RD) histone pre-mRNA processing requires association with a stem-loop (SL) motif and a histone downstream element (HDE), and produces cleaved but non-polyadenylated mature mRNAs. H2AC18 mRNA, a specific H2A RD histone pre-mRNA, can be processed to give either a non-polyadenylated mRNA, ending at the histone SL, or a polyadenylated mRNA. Here, we reveal how H2AC18 captures the two human pre-mRNA processing complexes in a mutually exclusive mode by overlapping a canonical PAS (AAUAAA) sequence element with a HDE. Disruption of the PAS sequence on H2AC18 pre-mRNA prevents recruitment of the canonical complex in vitro, without affecting the histone machinery. This shows how the relative position of cis-acting elements in histone pre-mRNAs allows the selective recruitment of distinct human pre-mRNA complexes, thereby expanding the capability to regulate 3' processing and polyadenylation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Caron2022b,

title = {Loss of SET1/COMPASS methyltransferase activity reduces lifespan and fertility in Caenorhabditis elegans},

author = {Matthieu Caron and Loïc Gely and Steven Garvis and Annie Adrait and Yohann Couté and Francesca Palladino and Paola Fabrizio},

doi = {10.26508/lsa.202101140},

issn = {2575-1077},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Life Science Alliance},

volume = {5},

issue = {3},

pages = {e202101140},

abstract = {Changes in histone post-translational modifications are associated with aging through poorly defined mechanisms. Histone 3 lysine 4 (H3K4) methylation at promoters is deposited by SET1 family methyltransferases acting within conserved multiprotein complexes known as COMPASS. Previous work yielded conflicting results about the requirement for H3K4 methylation during aging. Here, we reassessed the role of SET1/COMPASS-dependent H3K4 methylation in Caenorhabditis elegans lifespan and fertility by generating set-2(syb2085) mutant animals that express a catalytically inactive form of SET-2, the C. elegans SET1 homolog. We show that set-2(syb2085) animals retain the ability to form COMPASS, but have a marked global loss of H3K4 di- and trimethylation (H3K4me2/3). Reduced H3K4 methylation was accompanied by loss of fertility, as expected; however, in contrast to earlier studies, set-2(syb2085) mutants displayed a significantly shortened, not extended, lifespan and had normal intestinal fat stores. Other commonly used set-2 mutants were also short-lived, as was a cfp-1 mutant that lacks the SET1/COMPASS chromatin-targeting component. These results challenge previously held views and establish that WT H3K4me2/3 levels are essential for normal lifespan in C. elegans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Targeted Proteomics Analysis of Staphylococcal Superantigenic Toxins in Menstrual Fluid from Women with Menstrual Toxic Shock Syndrome (mTSS)},

author = {Marie Courçon and Cédric Badiou and Mathilde Louwagie and Sibyle Etievant and Michel Jaquinod and Gérard Lina and Virginie Brun},

url = {https://www.mdpi.com/2072-6651/14/12/886},

doi = {10.3390/toxins14120886},

issn = {2072-6651},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Toxins},

volume = {14},

issue = {12},

pages = {886},

abstract = {Menstrual toxic shock syndrome (mTSS) is a rare life-threatening febrile illness that occurs in women using intravaginal menstrual protection. It is caused by toxic shock syndrome toxin 1 (TSST-1) produced by Staphylococcus aureus, triggering a sudden onset of rash and hypotension, subsequently leading to multiple organ failure. Detecting TSST-1 and S. aureus virulence factors in menstrual fluid could accelerate the diagnosis and improve therapeutic management of mTSS. However, menstrual fluid is a highly complex matrix, making detection of bacterial toxins challenging. Here, we present a mass-spectrometry-based proteomics workflow for the targeted, quantitative analysis of four S. aureus superantigenic toxins in menstrual fluids (TSST-1, SEA, SEC, and SED). This method was applied to characterize toxin levels in menstrual fluids collected from patients with mTSS and healthy women. Toxins were detectable in samples from patients with mTSS and one healthy donor at concentrations ranging from 0 to 0.46 µg/mL for TSST-1, and 0 to 1.07 µg/mL for SEC. SEA and SED were never detected in clinical specimens, even though many S. aureus strains were positive for the corresponding genes. The method presented here could be used to explore toxin production in vivo in users of intravaginal devices to improve the diagnosis, understanding, and prevention of mTSS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lai2022b,

title = {Characterizing Nanoparticle Mass Distributions Using Charge-Independent Nanoresonator Mass Spectrometry},

author = {Szu-Hsueh Lai and Adrien Reynaud and Ning-Ning Zhang and Minjeong Kwak and Bogdan Vysotskyi and Sergio Dominguez-Medina and Thomas Fortin and Kavya Clement and Martial Defoort and Tae Geol Lee and Kun Liu and Sébastien Hentz and Christophe D Masselon},

url = {https://pubs.acs.org/doi/10.1021/acs.jpcc.2c06675},

doi = {10.1021/acs.jpcc.2c06675},

issn = {1932-7447, 1932-7455},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {The Journal of Physical Chemistry C},

volume = {126},

issue = {49},

pages = {20946-20953},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Etourneau2022b,

title = {Challenging Targets or Describing Mismatches? A Comment on Common Decoy Distribution by Madej et al},

author = {Lucas Etourneau and Thomas Burger},

doi = {10.1021/acs.jproteome.2c00279},

issn = {1535-3907},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Journal of Proteome Research},

volume = {21},

issue = {12},

pages = {2840-2845},

abstract = {In their recent article, Madej et al. (Madej, D.; Wu, L.; Lam, H.Common Decoy Distributions Simplify False Discovery Rate Estimation in Shotgun Proteomics. J. Proteome Res.2022, 21 (2), 339-348) proposed an original way to solve the recurrent issue of controlling for the false discovery rate (FDR) in peptide-spectrum-match (PSM) validation. Briefly, they proposed to derive a single precise distribution of decoy matches termed the Common Decoy Distribution (CDD) and to use it to control for FDR during a target-only search. Conceptually, this approach is appealing as it takes the best of two worlds, i.e., decoy-based approaches (which leverage a large-scale collection of empirical mismatches) and decoy-free approaches (which are not subject to the randomness of decoy generation while sparing an additional database search). Interestingly, CDD also corresponds to a middle-of-the-road approach in statistics with respect to the two main families of FDR control procedures: Although historically based on estimating the false-positive distribution, FDR control has recently been demonstrated to be possible thanks to competition between the original variables (in proteomics, target sequences) and their fictional counterparts (in proteomics, decoys). Discriminating between these two theoretical trends is of prime importance for computational proteomics. In addition to highlighting why proteomics was a source of inspiration for theoretical biostatistics, it provides practical insights into the improvements that can be made to FDR control methods used in proteomics, including CDD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Timcheva2022b,

title = {Chromatin-associated YTHDC1 coordinates heat-induced reprogramming of gene expression},

author = {Kalina Timcheva and Solenne Dufour and Leila Touat-Todeschini and Callum Burnard and Marie-Christine Carpentier and Florent Chuffart and Rémy Merret and Marion Helsmoortel and Sabrina Ferré and Aude Grézy and Yohann Couté and Sophie Rousseaux and Saadi Khochbin and Claire Vourc’h and Cécile Bousquet-Antonelli and Rosemary Kiernan and Daphné Seigneurin-Berny and André Verdel},

url = {https://linkinghub.elsevier.com/retrieve/pii/S2211124722016722},

doi = {10.1016/j.celrep.2022.111784},

issn = {22111247},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Cell Reports},

volume = {41},

issue = {11},

pages = {111784},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lupette2022b,

title = {Quantitative proteomic analyses reveal the impact of nitrogen starvation on the proteome of the model diatom Phaeodactylum tricornutum},

author = {Josselin Lupette and Marianne Tardif and Sabine Brugière and Yohann Couté and Juliette Salvaing and Eric Maréchal},

doi = {10.1002/pmic.202200155},

issn = {1615-9861},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Proteomics},

volume = {22},

issue = {22},

pages = {e2200155},

abstract = {Diatoms are one of the largest groups in phytoplankton biodiversity. Understanding their response to nitrogen variations, present from micromolar to near-zero levels in oceans and fresh waters, is essential to comprehend their ecological success. Nitrogen starvation is used in biotechnological processes, to trigger the remodeling of carbon metabolism in the direction of fatty acids and triacylglycerol synthesis. We evaluated whole proteome changes in Phaeodactylum tricornutum after 7 days of cultivation with 5.5-mM nitrate (+N) or without any nitrogen source (-N). On a total of 3768 proteins detected in biological replicates, our analysis pointed to 384 differentially abundant proteins (DAP). Analysis of proteins of lower abundance in -N revealed an arrest of amino acid and protein syntheses, a remodeling of nitrogen metabolism, and a decrease of the proteasome abundance suggesting a decline in unselective whole-proteome decay. Analysis of proteins of higher abundance revealed the setting up of a general nitrogen scavenging system dependent on deaminases. The increase of a plastid palmitoyl-ACP desaturase appeared as a hallmark of carbon metabolism rewiring in the direction of fatty acid and triacylglycerol synthesis. This dataset is also valuable to select gene candidates for improved biotechnological properties.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Leisico2022b,

title = {Structure of the human heparan sulfate polymerase complex EXT1-EXT2},

author = {Francisco Leisico and Juneina Omeiri and Christine Le Narvor and Joël Beaudouin and Michael Hons and Daphna Fenel and Guy Schoehn and Yohann Couté and David Bonnaffé and Rabia Sadir and Hugues Lortat-Jacob and Rebekka Wild},

doi = {10.1038/s41467-022-34882-6},

issn = {2041-1723},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nature Communications},

volume = {13},

issue = {1},

pages = {7110},

abstract = {Heparan sulfates are complex polysaccharides that mediate the interaction with a broad range of protein ligands at the cell surface. A key step in heparan sulfate biosynthesis is catalyzed by the bi-functional glycosyltransferases EXT1 and EXT2, which generate the glycan backbone consisting of repeating N-acetylglucosamine and glucuronic acid units. The molecular mechanism of heparan sulfate chain polymerization remains, however, unknown. Here, we present the cryo-electron microscopy structure of human EXT1-EXT2, which reveals the formation of a tightly packed hetero-dimeric complex harboring four glycosyltransferase domains. A combination of in vitro and in cellulo mutational studies is used to dissect the functional role of the four catalytic sites. While EXT1 can catalyze both glycosyltransferase reactions, our results indicate that EXT2 might only have N-acetylglucosamine transferase activity. Our findings provide mechanistic insight into heparan sulfate chain elongation as a nonprocessive process and lay the foundation for future studies on EXT1-EXT2 function in health and disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {The Toxoplasma effector GRA28 promotes parasite dissemination by inducing dendritic cell-like migratory properties in infected macrophages},

author = {Arne L Ten Hoeve and Laurence Braun and Matias E Rodriguez and Gabriela C Olivera and Alexandre Bougdour and Lucid Belmudes and Yohann Couté and Jeroen P J Saeij and Mohamed-Ali Hakimi and Antonio Barragan},

doi = {10.1016/j.chom.2022.10.001},

issn = {1934-6069},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Cell Host & Microbe},

volume = {30},

issue = {11},

pages = {1570–1588.e7},

abstract = {Upon pathogen detection, macrophages normally stay sessile in tissues while dendritic cells (DCs) migrate to secondary lymphoid tissues. The obligate intracellular protozoan Toxoplasma gondii exploits the trafficking of mononuclear phagocytes for dissemination via unclear mechanisms. We report that, upon T. gondii infection, macrophages initiate the expression of transcription factors normally attributed to DCs, upregulate CCR7 expression with a chemotactic response, and perform systemic migration when adoptively transferred into mice. We show that parasite effector GRA28, released by the MYR1 secretory pathway, cooperates with host chromatin remodelers in the host cell nucleus to drive the chemotactic migration of parasitized macrophages. During in vivo challenge studies, bone marrow-derived macrophages infected with wild-type T. gondii outcompeted those challenged with MYR1- or GRA28-deficient strains in migrating and reaching secondary organs. This work reveals how an intracellular parasite hijacks chemotaxis in phagocytes and highlights a remarkable migratory plasticity in differentiated cells of the mononuclear phagocyte system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Abulfaraj2022b,

title = {Analysis of the Arabidopsis coilin mutant reveals a positive role of AtCOILIN in plant immunity},

author = {Aala A Abulfaraj and Hanna M Alhoraibi and Kiruthiga Mariappan and Jean Bigeard and Huoming Zhang and Marilia Almeida-Trapp and Olga Artyukh and Fatimah Abdulhakim and Sabiha Parween and Delphine Pflieger and Ikram Blilou and Heribert Hirt and Naganand Rayapuram},

doi = {10.1093/plphys/kiac280},

issn = {1532-2548},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Plant Physiology},

volume = {190},

issue = {1},

pages = {745-761},

abstract = {Biogenesis of ribonucleoproteins occurs in dynamic subnuclear compartments called Cajal bodies (CBs). COILIN is a critical scaffolding component essential for CB formation, composition, and activity. We recently showed that Arabidopsis (Arabidopsis thaliana) AtCOILIN is phosphorylated in response to bacterial elicitor treatment. Here, we further investigated the role of AtCOILIN in plant innate immunity. Atcoilin mutants are compromised in defense responses to bacterial pathogens. Besides confirming a role of AtCOILIN in alternative splicing (AS), Atcoilin showed differential expression of genes that are distinct from those of AS, including factors involved in RNA biogenesis, metabolism, plant immunity, and phytohormones. Atcoilin mutant plants have reduced levels of defense phytohormones. As expected, the mutant plants were more sensitive to the necrotrophic fungal pathogen Botrytis cinerea. Our findings reveal an important role for AtCOILIN in innate plant immunity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fancello2022b,

title = {An analysis of proteogenomics and how and when transcriptome-informed reduction of protein databases can enhance eukaryotic proteomics},

author = {Laura Fancello and Thomas Burger},

doi = {10.1186/s13059-022-02701-2},

issn = {1474-760X},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Genome Biology},

volume = {23},

issue = {1},

pages = {132},

abstract = {BACKGROUND: Proteogenomics aims to identify variant or unknown proteins in bottom-up proteomics, by searching transcriptome- or genome-derived custom protein databases. However, empirical observations reveal that these large proteogenomic databases produce lower-sensitivity peptide identifications. Various strategies have been proposed to avoid this, including the generation of reduced transcriptome-informed protein databases, which only contain proteins whose transcripts are detected in the sample-matched transcriptome. These were found to increase peptide identification sensitivity. Here, we present a detailed evaluation of this approach. RESULTS: We establish that the increased sensitivity in peptide identification is in fact a statistical artifact, directly resulting from the limited capability of target-decoy competition to accurately model incorrect target matches when using excessively small databases. As anti-conservative false discovery rates (FDRs) are likely to hamper the robustness of the resulting biological conclusions, we advocate for alternative FDR control methods that are less sensitive to database size. Nevertheless, reduced transcriptome-informed databases are useful, as they reduce the ambiguity of protein identifications, yielding fewer shared peptides. Furthermore, searching the reference database and subsequently filtering proteins whose transcripts are not expressed reduces protein identification ambiguity to a similar extent, but is more transparent and reproducible. CONCLUSIONS: In summary, using transcriptome information is an interesting strategy that has not been promoted for the right reasons. While the increase in peptide identifications from searching reduced transcriptome-informed databases is an artifact caused by the use of an FDR control method unsuitable to excessively small databases, transcriptome information can reduce the ambiguity of protein identifications.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Spontaneous Prophage Induction Contributes to the Production of Membrane Vesicles by the Gram-Positive Bacterium Lacticaseibacillus casei BL23},

author = {David Silva Barreira and Pierre Lapaquette and Julia Novion Ducassou and Yohann Couté and Jean Guzzo and Aurélie Rieu},

doi = {10.1128/mbio.02375-22},

issn = {2150-7511},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {mBio},

volume = {13},

issue = {5},

pages = {e0237522},

abstract = {The formation of membrane vesicles (MVs) by Gram-positive bacteria has gained increasing attention over the last decade. Recently, models of vesicle formation have been proposed and involve the digestion of the cell wall by prophage-encoded or stress-induced peptidoglycan (PG) hydrolases and the inhibition of PG synthesis by β-lactam antibiotics. The impact of these mechanisms on vesicle formation is largely dependent on the strain and growth conditions. To date, no information on the production of vesicles by the lactobacilli family has been reported. Here, we aimed to characterize the MVs released by the Gram-positive bacteria Lacticaseibacillus casei BL23 and also investigated the mechanisms involved in vesicle formation. Using electron microscopy, we established that the size of the majority of L. casei BL23 vesicles ranged from 50 to 100 nm. Furthermore, we showed that the vesicles were released consistently throughout the growth of the bacteria in standard culture conditions. The protein composition of the vesicles released in the supernatant was identified and a significant number of prophage proteins was detected. Moreover, using a mutant strain harboring a defective PLE2 prophage, we were able to show that the spontaneous and mitomycin-triggered induction of the prophage PLE2 contribute to the production of MVs by L. casei BL23. Finally, we also demonstrated the influence of prophages on the membrane integrity of bacteria. Overall, our results suggest a key role of the prophage PLE2 in the production of MVs by L. casei BL23 in the absence or presence of genotoxic stress. IMPORTANCE The last few decades have demonstrated that membrane vesicles (MVs) produced by microorganisms can have a wide variety of functions. This diversity places MVs at the crossroads of major research topics in current microbiology such as antibiotic resistance, horizontal gene transfer, cell communication, biofilm development, bacteriophage resistance, and pathogenesis. In particular, vesicles produced by probiotic strains have been shown to play a significant role in their beneficial effects. Thus, the study of vesicle biogenesis is a key element for promoting and improving their release. Overall, our results suggest a key role of spontaneous and mitomycin-triggered prophage induction in MV production by the Gram-positive bacteria Lacticaseibacillus casei BL23. This phenomenon is of great interest as prophage-induced MVs could potentially influence bacterial behavior, stress resistance, and vesicle functions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lacroux2022b,

title = {Proteomics unveil a central role for peroxisomes in butyrate assimilation of the heterotrophic Chlorophyte alga Polytomella sp.},

author = {Julien Lacroux and Ariane Atteia and Sabine Brugière and Yohann Couté and Olivier Vallon and Jean-Philippe Steyer and Robert Lis},

url = {https://www.frontiersin.org/articles/10.3389/fmicb.2022.1029828/full},

doi = {10.3389/fmicb.2022.1029828},

issn = {1664-302X},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Frontiers in Microbiology},

volume = {13},

pages = {1029828},

abstract = {Volatile fatty acids found in effluents of the dark fermentation of biowastes can be used for mixotrophic growth of microalgae, improving productivity and reducing the cost of the feedstock. Microalgae can use the acetate in the effluents very well, but butyrate is poorly assimilated and can inhibit growth above 1 gC.L −1 . The non-photosynthetic chlorophyte alga Polytomella sp. SAG 198.80 was found to be able to assimilate butyrate fast. To decipher the metabolic pathways implicated in butyrate assimilation, quantitative proteomics study was developed comparing Polytomella sp. cells grown on acetate and butyrate at 1 gC.L −1 . After statistical analysis, a total of 1772 proteins were retained, of which 119 proteins were found to be overaccumulated on butyrate vs. only 46 on acetate, indicating that butyrate assimilation necessitates additional metabolic steps. The data show that butyrate assimilation occurs in the peroxisome via the β-oxidation pathway to produce acetyl-CoA and further tri/dicarboxylic acids in the glyoxylate cycle. Concomitantly, reactive oxygen species defense enzymes as well as the branched amino acid degradation pathway were strongly induced. Although no clear dedicated butyrate transport mechanism could be inferred, several membrane transporters induced on butyrate are identified as potential condidates. Metabolic responses correspond globally to the increased needs for central cofactors NAD, ATP and CoA, especially in the peroxisome and the cytosol.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vilallongue2022b,

title = {Guidance landscapes unveiled by quantitative proteomics to control reinnervation in adult visual system},

author = {Noemie Vilallongue and Julia Schaeffer and Anne-Marie Hesse and Céline Delpech and Béatrice Blot and Antoine Paccard and Elise Plissonnier and Blandine Excoffier and Yohann Couté and Stephane Belin and Homaira Nawabi},

url = {https://www.nature.com/articles/s41467-022-33799-4},

doi = {10.1038/s41467-022-33799-4},

issn = {2041-1723},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nature Communications},

volume = {13},

issue = {1},

pages = {6040},

abstract = {Abstract In the injured adult central nervous system (CNS), activation of pro-growth molecular pathways in neurons leads to long-distance regeneration. However, most regenerative fibers display guidance defects, which prevent reinnervation and functional recovery. Therefore, the molecular characterization of the proper target regions of regenerative axons is essential to uncover the modalities of adult reinnervation. In this study, we use mass spectrometry (MS)-based quantitative proteomics to address the proteomes of major nuclei of the adult visual system. These analyses reveal that guidance-associated molecules are expressed in adult visual targets. Moreover, we show that bilateral optic nerve injury modulates the expression of specific proteins. In contrast, the expression of guidance molecules remains steady. Finally, we show that regenerative axons are able to respond to guidance cues ex vivo, suggesting that these molecules possibly interfere with brain target reinnervation in adult. Using a long-distance regeneration model, we further demonstrate that the silencing of specific guidance signaling leads to rerouting of regenerative axons in vivo. Altogether, our results suggest ways to modulate axon guidance of regenerative neurons to achieve circuit repair in adult.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Barnault2022b,

title = {Hepatic inflammation elicits production of proinflammatory netrin-1 through exclusive activation of translation},

author = {Romain Barnault and Claire Verzeroli and Carole Fournier and Maud Michelet and Anna Rita Redavid and Ievgeniia Chicherova and Marie-Laure Plissonnier and Annie Adrait and Olga Khomich and Fleur Chapus and Mathieu Richaud and Maëva Hervieu and Veronika Reiterer and Federica Grazia Centonze and Julie Lucifora and Birke Bartosch and Michel Rivoire and Hesso Farhan and Yohann Couté and Valbona Mirakaj and Thomas Decaens and Patrick Mehlen and Benjamin Gibert and Fabien Zoulim and Romain Parent},

doi = {10.1002/hep.32446},

issn = {1527-3350},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Hepatology (Baltimore, Md.)},

volume = {76},

issue = {5},

pages = {1345-1359},

abstract = {BACKGROUND AND AIMS: Netrin-1 displays protumoral properties, though the pathological contexts and processes involved in its induction remain understudied. The liver is a major model of inflammation-associated cancer development, leading to HCC. APPROACH AND RESULTS: A panel of cell biology and biochemistry approaches (reverse transcription quantitative polymerase chain reaction, reporter assays, run-on, polysome fractionation, cross linking immunoprecipitation, filter binding assay, subcellular fractionation, western blotting, immunoprecipitation, stable isotope labeling by amino acids in cell culture) on in vitro-grown primary hepatocytes, human liver cell lines, mouse samples and clinical samples was used. We identify netrin-1 as a hepatic inflammation-inducible factor and decipher its mode of activation through an exhaustive eliminative approach. We show that netrin-1 up-regulation relies on a hitherto unknown mode of induction, namely its exclusive translational activation. This process includes the transfer of NTN1 (netrin-1) mRNA to the endoplasmic reticulum and the direct interaction between the Staufen-1 protein and this transcript as well as netrin-1 mobilization from its cell-bound form. Finally, we explore the impact of a phase 2 clinical trial-tested humanized anti-netrin-1 antibody (NP137) in two distinct, toll-like receptor (TLR) 2/TLR3/TLR6-dependent, hepatic inflammatory mouse settings. We observe a clear anti-inflammatory activity indicating the proinflammatory impact of netrin-1 on several chemokines and Ly6C+ macrophages. CONCLUSIONS: These results identify netrin-1 as an inflammation-inducible factor in the liver through an atypical mechanism as well as its contribution to hepatic inflammation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Villalta2022b,

title = {The giant mimivirus 1.2 Mb genome is elegantly organized into a 30-nm diameter helical protein shield},

author = {Alejandro Villalta and Alain Schmitt and Leandro F Estrozi and Emmanuelle R J Quemin and Jean-Marie Alempic and Audrey Lartigue and Vojtěch Pražák and Lucid Belmudes and Daven Vasishtan and Agathe M G Colmant and Flora A Honoré and Yohann Couté and Kay Grünewald and Chantal Abergel},

doi = {10.7554/eLife.77607},

issn = {2050-084X},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {eLife},

volume = {11},

pages = {e77607},

abstract = {Mimivirus is the prototype of the Mimiviridae family of giant dsDNA viruses. Little is known about the organization of the 1.2 Mb genome inside the membrane-limited nucleoid filling the textasciitilde0.5 µm icosahedral capsids. Cryo-electron microscopy, cryo-electron tomography, and proteomics revealed that it is encased into a textasciitilde30-nm diameter helical protein shell surprisingly composed of two GMC-type oxidoreductases, which also form the glycosylated fibrils decorating the capsid. The genome is arranged in 5- or 6-start left-handed super-helices, with each DNA-strand lining the central channel. This luminal channel of the nucleoprotein fiber is wide enough to accommodate oxidative stress proteins and RNA polymerase subunits identified by proteomics. Such elegant supramolecular organization would represent a remarkable evolutionary strategy for packaging and protecting the genome, in a state ready for immediate transcription upon unwinding in the host cytoplasm. The parsimonious use of the same protein in two unrelated substructures of the virion is unexpected for a giant virus with thousand genes at its disposal.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {SMYD3 Impedes Small Cell Lung Cancer Sensitivity to Alkylation Damage through RNF113A Methylation-Phosphorylation Cross-talk},

author = {Valentina Lukinović and Simone Hausmann and Gael S Roth and Clement Oyeniran and Tanveer Ahmad and Ning Tsao and Joshua R Brickner and Alexandre G Casanova and Florent Chuffart and Ana Morales Benitez and Jessica Vayr and Rebecca Rodell and Marianne Tardif and Pascal W T C Jansen and Yohann Couté and Michiel Vermeulen and Pierre Hainaut and Pawel K Mazur and Nima Mosammaparast and Nicolas Reynoird},

doi = {10.1158/2159-8290.CD-21-0205},

issn = {2159-8290},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Cancer Discovery},

volume = {12},

issue = {9},

pages = {2158-2179},

abstract = {Small cell lung cancer (SCLC) is the most fatal form of lung cancer, with dismal survival, limited therapeutic options, and rapid development of chemoresistance. We identified the lysine methyltransferase SMYD3 as a major regulator of SCLC sensitivity to alkylation-based chemotherapy. RNF113A methylation by SMYD3 impairs its interaction with the phosphatase PP4, controlling its phosphorylation levels. This cross-talk between posttranslational modifications acts as a key switch in promoting and maintaining RNF113A E3 ligase activity, essential for its role in alkylation damage response. In turn, SMYD3 inhibition restores SCLC vulnerability to alkylating chemotherapy. Our study sheds light on a novel role of SMYD3 in cancer, uncovering this enzyme as a mediator of alkylation damage sensitivity and providing a rationale for small-molecule SMYD3 inhibition to improve responses to established chemotherapy. SIGNIFICANCE: SCLC rapidly becomes resistant to conventional chemotherapy, leaving patients with no alternative treatment options. Our data demonstrate that SMYD3 upregulation and RNF113A methylation in SCLC are key mechanisms that control the alkylation damage response. Notably, SMYD3 inhibition sensitizes cells to alkylating agents and promotes sustained SCLC response to chemotherapy. This article is highlighted in the In This Issue feature, p. 2007.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ruedas2022b,

title = {Three-Dimensional Envelope and Subunit Interactions of the Plastid-Encoded RNA Polymerase from Sinapis alba},

author = {Rémi Ruedas and Soumiya Sankari Muthukumar and Sylvie Kieffer-Jaquinod and François-Xavier Gillet and Daphna Fenel and Grégory Effantin and Thomas Pfannschmidt and Yohann Couté and Robert Blanvillain and David Cobessi},

url = {https://www.mdpi.com/1422-0067/23/17/9922},

doi = {10.3390/ijms23179922},

issn = {1422-0067},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

issue = {17},

pages = {9922},

abstract = {RNA polymerases (RNAPs) are found in all living organisms. In the chloroplasts, the plastid-encoded RNA polymerase (PEP) is a prokaryotic-type multimeric RNAP involved in the selective transcription of plastid genome. One of its active states requires the assembly of nuclear-encoded PEP-Associated Proteins (PAPs) on the catalytic core, producing a complex of more than 900 kDa, regarded as essential for chloroplast biogenesis. In this study, sequence alignments of the catalytic core subunits across various chloroplasts of the green lineage and prokaryotes combined with structural data show that variations are observed at the surface of the core, whereas internal amino acids associated with the catalytic activity are conserved. A purification procedure compatible with a structural analysis was used to enrich the native PEP from Sinapis alba chloroplasts. A mass spectrometry (MS)-based proteomic analysis revealed the core components, the PAPs and additional proteins, such as FLN2 and pTAC18. MS coupled with crosslinking (XL-MS) provided the initial structural information in the form of protein clusters, highlighting the relative position of some subunits with the surfaces of their interactions. Using negative stain electron microscopy, the PEP three-dimensional envelope was calculated. Particles classification shows that the protrusions are very well-conserved, offering a framework for the future positioning of all the PAPs. Overall, the results show that PEP-associated proteins are firmly and specifically associated with the catalytic core, giving to the plastid transcriptional complex a singular structure compared to other RNAPs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Filhol2022b,

title = {CK2β Is a Gatekeeper of Focal Adhesions Regulating Cell Spreading},

author = {Odile Filhol and Anne-Marie Hesse and Anne-Pascale Bouin and Corinne Albigès-Rizo and Florian Jeanneret and Christophe Battail and Delphine Pflieger and Claude Cochet},

doi = {10.3389/fmolb.2022.900947},

issn = {2296-889X},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Frontiers in Molecular Biosciences},

volume = {9},

pages = {900947},

abstract = {CK2 is a hetero-tetrameric serine/threonine protein kinase made up of two CK2α/α' catalytic subunits and two CK2β regulatory subunits. The free CK2α subunit and the tetrameric holoenzyme have distinct substrate specificity profiles, suggesting that the spatiotemporal organization of the individual CK2 subunits observed in living cells is crucial in the control of the many cellular processes that are governed by this pleiotropic kinase. Indeed, previous studies reported that the unbalanced expression of CK2 subunits is sufficient to drive epithelial to mesenchymal transition (EMT), a process involved in cancer invasion and metastasis. Moreover, sub-stoichiometric expression of CK2β compared to CK2α in a subset of breast cancer tumors was correlated with the induction of EMT markers and increased epithelial cell plasticity in breast carcinoma progression. Phenotypic changes of epithelial cells are often associated with the activation of phosphotyrosine signaling. Herein, using phosphotyrosine enrichment coupled with affinity capture and proteomic analysis, we show that decreased expression of CK2β in MCF10A mammary epithelial cells triggers the phosphorylation of a number of proteins on tyrosine residues and promotes the striking activation of the FAK1-Src-PAX1 signaling pathway. Moreover, morphometric analyses also reveal that CK2β loss increases the number and the spatial distribution of focal adhesion signaling complexes that coordinate the adhesive and migratory processes. Together, our findings allow positioning CK2β as a gatekeeper for cell spreading by restraining focal adhesion formation and invasion of mammary epithelial cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nyonda2022b,

title = {N-acetylation of secreted proteins in Apicomplexa is widespread and is independent of the ER acetyl-CoA transporter AT1},

author = {Mary Akinyi Nyonda and Jean-Baptiste Boyer and Lucid Belmudes and Aarti Krishnan and Paco Pino and Yohann Couté and Mathieu Brochet and Thierry Meinnel and Dominique Soldati-Favre and Carmela Giglione},

doi = {10.1242/jcs.259811},

issn = {1477-9137},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Journal of Cell Science},

volume = {135},

issue = {15},

pages = {jcs259811},

abstract = {Acetyl-CoA participates in post-translational modification of proteins and in central carbon and lipid metabolism in several cell compartments. In mammals, acetyl-CoA transporter 1 (AT1, also known as SLC33A1) facilitates the flux of cytosolic acetyl-CoA into the endoplasmic reticulum (ER), enabling the acetylation of proteins of the secretory pathway, in concert with the activity of dedicated acetyltransferases such as NAT8. However, the involvement of the ER acetyl-CoA pool in acetylation of ER-transiting proteins in Apicomplexa is unknown. Here, we identified homologs of AT1 and NAT8 in Toxoplasma gondii and Plasmodium berghei parasites. Proteome-wide analyses revealed widespread N-terminal acetylation of secreted proteins in both species. Such extensive acetylation of N-terminally processed proteins has not been observed previously in any other organism. Deletion of AT1 homologs in both T. gondii and P. berghei resulted in considerable reductions in parasite fitness. In P. berghei, AT1 was found to be important for growth of asexual blood stages, production of female gametocytes and male gametocytogenesis, implying its requirement for parasite transmission. In the absence of AT1, lysine acetylation and N-terminal acetylation in T. gondii remained globally unaltered, suggesting an uncoupling between the role of AT1 in development and active acetylation occurring along the secretory pathway.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Job2022b,

title = {Genomic erosion and horizontal gene transfer shape functional differences of the ExlA toxin in Pseudomonas spp},

author = {Viviana Job and Laura Gomez-Valero and Adèle Renier and Christophe Rusniok and Stephanie Bouillot and Viviane Chenal-Francisque and Erwan Gueguen and Annie Adrait and Mylène Robert-Genthon and Katy Jeannot and Peter Panchev and Sylvie Elsen and Marie-Odile Fauvarque and Yohann Couté and Carmen Buchrieser and Ina Attrée},

doi = {10.1016/j.isci.2022.104596},

issn = {2589-0042},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {iScience},

volume = {25},

issue = {7},

pages = {104596},

abstract = {Two-partner secretion (TPS) is widespread in the bacterial world. The pore-forming TPS toxin ExlA of Pseudomonas aeruginosa is conserved in pathogenic and environmental Pseudomonas. While P. chlororaphis and P. entomophila displayed ExlA-dependent killing, P. putida did not cause damage to eukaryotic cells. ExlA proteins interacted with epithelial cell membranes; however, only ExlA Pch induced the cleavage of the adhesive molecule E-cadherin. ExlA proteins participated in insecticidal activity toward the larvae of Galleria mellonella and the fly Drosophila melanogaster. Evolutionary analyses demonstrated that the differences in the C-terminal domains are partly due to horizontal movements of the operon within the genus Pseudomonas. Reconstruction of the evolutionary history revealed the complex horizontal acquisitions. Together, our results provide evidence that conserved TPS toxins in environmental Pseudomonas play a role in bacteria-insect interactions and discrete differences in CTDs may determine their specificity and mode of action toward eukaryotic cells.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Swale2022b,

title = {Altiratinib blocks Toxoplasma gondii and Plasmodium falciparum development by selectively targeting a spliceosome kinase},

author = {Christopher Swale and Valeria Bellini and Matthew W Bowler and Nardella Flore and Marie-Pierre Brenier-Pinchart and Dominique Cannella and Lucid Belmudes and Caroline Mas and Yohann Couté and Fabrice Laurent and Artur Scherf and Alexandre Bougdour and Mohamed-Ali Hakimi},

url = {https://www.science.org/doi/10.1126/scitranslmed.abn3231},

doi = {10.1126/scitranslmed.abn3231},

issn = {1946-6234, 1946-6242},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Science Translational Medicine},

volume = {14},

issue = {656},

pages = {eabn3231},

abstract = {The Apicomplexa comprise a large phylum of single-celled, obligate intracellular protozoa that include Toxoplasma gondii , Plasmodium , and Cryptosporidium spp., which infect humans and animals and cause severe parasitic diseases. Available therapeutics against these diseases are limited by suboptimal efficacy and frequent side effects, as well as the emergence and spread of resistance. We use a drug repurposing strategy and identify altiratinib, a compound originally developed to treat glioblastoma, as a promising drug candidate with broad spectrum activity against apicomplexans. Altiratinib is parasiticidal and blocks the development of intracellular zoites in the nanomolar range and with a high selectivity index when used against T. gondii . We have identified Tg PRP4K of T. gondii as the primary target of altiratinib using genetic target deconvolution, which highlighted key residues within the kinase catalytic site that conferred drug resistance when mutated. We have further elucidated the molecular basis of the inhibitory mechanism and species selectivity of altiratinib for Tg PRP4K and for its Plasmodium falciparum counterpart, Pf CLK3. Our data identified structural features critical for binding of the other Pf CLK3 inhibitor, TCMDC-135051. Consistent with the splicing control activity of this kinase family, we have shown that altiratinib can cause global disruption of splicing, primarily through intron retention in both T. gondii and P. falciparum . Thus, our data establish parasitic PRP4K/CLK3 as a potential pan-apicomplexan target whose repertoire of inhibitors can be expanded by the addition of altiratinib. , Spliceosome targeting by altiratinib leads to Toxoplasma and Plasmodium inhibition. , Repurposing against parasites Toxoplasma gondii and Plasmodium falciparum are members of the Apicomplexa phylum of parasitic protists that can cause severe infections in humans and other animals. Available drugs against these parasites have limited efficacy and undesirable side effects. Swale et al. used a drug repurposing screen and identified altiratinib as a potential antiparasitic drug. Altiratinib was originally developed as a drug to treat glioblastoma, and, here, they show that this drug has potent parasiticidal activation against T. gondii . Through drug resistance screening and genetic target deconvolution, Tg PRP4K of T. gondii was identified as the primary target of altiratinib, which was confirmed for its counterpart in P. falciparum , Pf CLK3. Altiratinib was shown to globally disrupt splicing by targeting this family of parasite kinases. These findings support further development of pan-apicomplexan inhibitors that target this pathway.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mladenov2022b,

title = {Proteomics Evidence of a Systemic Response to Desiccation in the Resurrection Plant Haberlea rhodopensis},

author = {Petko Mladenov and Diana Zasheva and Sébastien Planchon and Céline C Leclercq and Denis Falconet and Lucas Moyet and Sabine Brugière and Daniela Moyankova and Magdalena Tchorbadjieva and Myriam Ferro and Norbert Rolland and Jenny Renaut and Dimitar Djilianov and Xin Deng},

url = {https://www.mdpi.com/1422-0067/23/15/8520},

doi = {10.3390/ijms23158520},

issn = {1422-0067},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

issue = {15},

pages = {8520},

abstract = {Global warming and drought stress are expected to have a negative impact on agricultural productivity. Desiccation-tolerant species, which are able to tolerate the almost complete desiccation of their vegetative tissues, are appropriate models to study extreme drought tolerance and identify novel approaches to improve the resistance of crops to drought stress. In the present study, to better understand what makes resurrection plants extremely tolerant to drought, we performed transmission electron microscopy and integrative large-scale proteomics, including organellar and phosphorylation proteomics, and combined these investigations with previously published transcriptomic and metabolomics data from the resurrection plant Haberlea rhodopensis. The results revealed new evidence about organelle and cell preservation, posttranscriptional and posttranslational regulation, photosynthesis, primary metabolism, autophagy, and cell death in response to desiccation in H. rhodopensis. Different protective intrinsically disordered proteins, such as late embryogenesis abundant (LEA) proteins, thaumatin-like proteins (TLPs), and heat shock proteins (HSPs), were detected. We also found a constitutively abundant dehydrin in H. rhodopensis whose phosphorylation levels increased under stress in the chloroplast fraction. This integrative multi-omics analysis revealed a systemic response to desiccation in H. rhodopensis and certain targets for further genomic and evolutionary studies on DT mechanisms and genetic engineering towards the improvement of drought tolerance in crops.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Direct visualization of pre-protamine 2 detects protamine assembly failures and predicts ICSI success},

author = {Maryam Rezaei-Gazik and Alexandra Vargas and Amir Amiri-Yekta and Anne-Laure Vitte and Arvand Akbari and Sophie Barral and Vahid Esmaeili and Florent Chuffart and Mohammad Ali Sadighi-Gilani and Yohann Couté and Poopak Eftekhari-Yazdi and Saadi Khochbin and Sophie Rousseaux and Mehdi Totonchi},

url = {https://academic.oup.com/molehr/article/doi/10.1093/molehr/gaac004/6527641},

doi = {10.1093/molehr/gaac004},

issn = {1360-9947, 1460-2407},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Molecular Human Reproduction},

volume = {28},

issue = {2},

pages = {gaac004},

abstract = {Abstract Histone-to-protamine transition is an essential step in the generation of fully functional spermatozoa in various mammalian species. In human and mouse, one of the two protamine-encoding genes produces a precursor pre-protamine 2 (pre-PRM2) protein, which is then processed and assembled. Here, we design an original approach based on the generation of pre-PRM2-specific antibodies to visualize the unprocessed pre-PRM2 by microscopy, flow cytometry and immunoblotting. Using mouse models with characterized failures in histone-to-protamine replacement, we show that pre-PRM2 retention is tightly linked to impaired nucleosome disassembly. Additionally, in elongating/condensing spermatids, we observe that pre-PRM2 and transition protein are co-expressed spatiotemporally, and their physical interaction suggests that these proteins act simultaneously rather than successively during histone replacement. By using our anti-human pre-PRM2 antibody, we also measured pre-PRM2 retention rates in the spermatozoa from 49 men of a series of infertile couples undergoing ICSI, which shed new light on the debated relation between pre-PRM2 retention and sperm parameters. Finally, by monitoring 2-pronuclei embryo formation following ICSI, we evaluated the fertilization ability of the sperm in these 49 patients. Our results suggest that the extent of pre-PRM2 retention in sperm, rather than pre-PRM2 accumulation per se, is associated with fertilization failure. Hence, anti-pre-PRM2 antibodies are valuable tools that could be used in routine monitoring of sperm parameters in fertility clinics, as well as in experimental research programmes to better understand the obscure process of histone-to-protamine transition.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gfrerer2022b,

title = {A Micrarchaeon Isolate Is Covered by a Proteinaceous S-Layer},

author = {Sabrina Gfrerer and Dennis Winkler and Julia Novion Ducassou and Yohann Couté and Reinhard Rachel and Johannes Gescher},

editor = {Nicole R Buan},

url = {https://journals.asm.org/doi/10.1128/aem.01553-21},

doi = {10.1128/aem.01553-21},

issn = {0099-2240, 1098-5336},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Applied and Environmental Microbiology},

volume = {88},

issue = {5},

pages = {e01553–21},

abstract = {Our knowledge about the DPANN superphylum, which comprises several archaeal phyla with limited metabolic capacities, is mostly based on genomic data derived from cultivation-independent approaches. This study examined the surface structure of a recently cultivated member “ Candidatus Micrarchaeum harzensis A_DKE,” an archaeal symbiont dependent on an interaction with a host organism for growth. , ABSTRACT In previous publications, it was hypothesized that Micrarchaeota cells are covered by two individual membrane systems. This study proves that at least the recently cultivated “ Candidatus Micrarchaeum harzensis A_DKE” possesses an S-layer covering its cytoplasmic membrane. The potential S-layer protein was found to be among the proteins with the highest abundance in “ Ca. Micrarchaeum harzensis A_DKE,” and in silico characterization of its primary structure indicated homologies to other known S-layer proteins. Homologues of this protein were found in other Micrarchaeota genomes, which raises the question of whether the ability to form an S-layer is a common trait within this phylum. The S-layer protein seems to be glycosylated, and the micrarchaeon expresses genes for N-glycosylation under cultivation conditions, despite not being able to synthesize carbohydrates. Electron micrographs of freeze-etched samples of a previously described coculture, containing “ Ca. Micrarchaeum harzensis A_DKE” and a Thermoplasmatales member as its host organism, verified the hypothesis of an S-layer on the surface of “ Ca. Micrarchaeum harzensis A_DKE.” Both organisms are clearly distinguishable by cell size, shape, and surface structure. IMPORTANCE Our knowledge about the DPANN superphylum, which comprises several archaeal phyla with limited metabolic capacities, is mostly based on genomic data derived from cultivation-independent approaches. This study examined the surface structure of a recently cultivated member “ Candidatus Micrarchaeum harzensis A_DKE,” an archaeal symbiont dependent on an interaction with a host organism for growth. The interaction requires direct cell contact between interaction partners, a mechanism which is also described for other DPANN archaea. Investigating the surface structure of “ Ca. Micrarchaeum harzensis A_DKE” is an important step toward understanding the interaction between Micrarchaeota and their host organisms and living with limited metabolic capabilities, a trait shared by several DPANN archaea.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vigetti2022b,

title = {The BCC7 Protein Contributes to the Toxoplasma Basal Pole by Interfacing between the MyoC Motor and the IMC Membrane Network},

author = {Luis Vigetti and Tatiana Labouré and Chloé Roumégous and Dominique Cannella and Bastien Touquet and Claudine Mayer and Yohann Couté and Karine Frénal and Isabelle Tardieux and Patricia Renesto},

url = {https://www.mdpi.com/1422-0067/23/11/5995},

doi = {10.3390/ijms23115995},

issn = {1422-0067},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

issue = {11},

pages = {5995},

abstract = {T. gondii is a eukaryotic parasite that has evolved a stage called tachyzoite which multiplies in host cells by producing two daughter cells internally. These nascent tachyzoites bud off their mother and repeat the division process until the expanding progenies escape to settle and multiply in other host cells. Over these intra- and extra-cellular phases, the tachyzoite maintains an essential apicobasal polarity that emerges through a unique bidirectional budding process of the elongating cells. This process requires the assembly of several molecular complexes that, at the nascent pole, encompass structural and myosin motor elements. To characterize a recently identified basal pole marker named BCC7 with respect to the posterior myosin J and myosin C motors, we used conventional biochemistry as well as advanced proteomic and in silico analysis in conjunction with live and super resolution microscopy of transgenic fluorescent tachyzoites. We document that BCC7 forms a ribbed ring below which myosin C motor entities distribute regularly. In addition, we identified—among 13 BCC7 putative partners—two novel and five known members of the inner membrane complex (IMC) family which ends at the apical side of the ring. Therefore, BCC7 could assist the stabilization of the IMC plaques and contribute to the parasite biomechanical properties.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Environmental cues from neural crest derivatives act as metastatic triggers in an embryonic neuroblastoma model},

author = {Dounia Ben Amar and Karine Thoinet and Benjamin Villalard and Olivier Imbaud and Clélia Costechareyre and Loraine Jarrosson and Florie Reynaud and Julia Novion Ducassou and Yohann Couté and Jean-François Brunet and Valérie Combaret and Nadège Corradini and Céline Delloye-Bourgeois and Valérie Castellani},

doi = {10.1038/s41467-022-30237-3},

issn = {2041-1723},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nature Communications},

volume = {13},

issue = {1},

pages = {2549},

abstract = {Embryonic malignant transformation is concomitant to organogenesis, often affecting multipotent and migratory progenitors. While lineage relationships between malignant cells and their physiological counterparts are extensively investigated, the contribution of exogenous embryonic signals is not fully known. Neuroblastoma (NB) is a childhood malignancy of the peripheral nervous system arising from the embryonic trunk neural crest (NC) and characterized by heterogeneous and interconvertible tumor cell identities. Here, using experimental models mimicking the embryonic context coupled to proteomic and transcriptomic analyses, we show that signals released by embryonic sympathetic ganglia, including Olfactomedin-1, induce NB cells to shift from a noradrenergic to mesenchymal identity, and to activate a gene program promoting NB metastatic onset and dissemination. From this gene program, we extract a core signature specifically shared by metastatic cancers with NC origin. This reveals non-cell autonomous embryonic contributions regulating the plasticity of NB identities and setting pro-dissemination gene programs common to NC-derived cancers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dragic2022b,

title = {The hexosamine pathway and coat complex II promote malignant adaptation to nutrient scarcity},

author = {Helena Dragic and Audrey Barthelaix and Cédric Duret and Simon Le Goupil and Hadrien Laprade and Sophie Martin and Sabine Brugière and Yohann Couté and Christelle Machon and Jerome Guitton and Justine Rudewicz and Paul Hofman and Serge Lebecque and Cedric Chaveroux and Carole Ferraro-Peyret and Toufic Renno and Serge N Manié},

doi = {10.26508/lsa.202101334},

issn = {2575-1077},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Life Science Alliance},

volume = {5},

issue = {7},

pages = {e202101334},

abstract = {The glucose-requiring hexosamine biosynthetic pathway (HBP), which produces UDP-N-acetylglucosamine for glycosylation reactions, promotes lung adenocarcinoma (LUAD) progression. However, lung tumor cells often reside in low-nutrient microenvironments, and whether the HBP is involved in the adaptation of LUAD to nutrient stress is unknown. Here, we show that the HBP and the coat complex II (COPII) play a key role in cell survival during glucose shortage. HBP up-regulation withstood low glucose-induced production of proteins bearing truncated N-glycans, in the endoplasmic reticulum. This function for the HBP, alongside COPII up-regulation, rescued cell surface expression of a subset of glycoproteins. Those included the epidermal growth factor receptor (EGFR), allowing an EGFR-dependent cell survival under low glucose in anchorage-independent growth. Accordingly, high expression of the HBP rate-limiting enzyme GFAT1 was associated with wild-type EGFR activation in LUAD patient samples. Notably, HBP and COPII up-regulation distinguished LUAD from the lung squamous-cell carcinoma subtype, thus uncovering adaptive mechanisms of LUAD to their harsh microenvironment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Permiakova2022b,

title = {Sketched Stochastic Dictionary Learning for large‐scale data and application to high‐throughput mass spectrometry},

author = {Olga Permiakova and Thomas Burger},

url = {https://onlinelibrary.wiley.com/doi/10.1002/sam.11542},

doi = {10.1002/sam.11542},

issn = {1932-1864, 1932-1872},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Statistical Analysis and Data Mining: The ASA Data Science Journal},

volume = {15},

issue = {1},

pages = {43-56},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Capizzi2022b,

title = {Developmental defects in Huntington's disease show that axonal growth and microtubule reorganization require NUMA1},

author = {Mariacristina Capizzi and Rémi Carpentier and Eric Denarier and Annie Adrait and Rayane Kassem and Marina Mapelli and Yohann Couté and Sandrine Humbert},

doi = {10.1016/j.neuron.2021.10.033},

issn = {1097-4199},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Neuron},

volume = {110},

issue = {1},

pages = {36–50.e5},

abstract = {Although the classic symptoms of Huntington's disease (HD) manifest in adulthood, neural progenitor cell behavior is already abnormal by 13 weeks' gestation. To determine how these developmental defects evolve, we turned to cell and mouse models. We found that layer II/III neurons that normally connect the hemispheres are limited in their growth in HD by microtubule bundling defects within the axonal growth cone, so that fewer axons cross the corpus callosum. Proteomic analyses of the growth cones revealed that NUMA1 (nuclear/mitotic apparatus protein 1) is downregulated in HD by miR-124. Suppressing NUMA1 in wild-type cells recapitulates the microtubule and axonal growth defects of HD, whereas raising NUMA1 levels with antagomiR-124 or stabilizing microtubules with epothilone B restores microtubule organization and rescues axonal growth. NUMA1 therefore regulates the microtubule network in the growth cone, and HD, which is traditionally conceived as a disease of intracellular trafficking, also disturbs the cytoskeletal network.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Arezki2022b,

title = {Surface charge influences protein corona, cell uptake and biological effects of carbon dots},

author = {Y Arezki and F Delalande and C Schaeffer-Reiss and S Cianferani and M Rapp and L Lebeau and F Pons and C Ronzani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36168840},

doi = {10.1039/d2nr03611h},

issn = {2040-3372 (Electronic) 2040-3364 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nanoscale},

abstract = {Carbon dots are emerging nanoparticles (NPs) with tremendous applications, especially in the biomedical field. Herein is reported the first quantitative proteomic analysis of the protein corona formed on CDs with different surface charge properties. Four CDs were synthesized from citric acid and various amine group-containing passivation reagents, resulting in cationic NPs with increasing zeta (zeta)-potential and density of positive charges. After CD contact with serum, we show that protein corona identity is influenced by CD surface charge properties, which in turn impacts CD uptake and viability loss in macrophages. In particular, CDs with high zeta-potential (+30 mV) and charge density (2 mumol mg(-1)) are the most highly internalized, and their cell uptake is strongly correlated with a corona enriched in vitronectin, fibulin, fetuin, adiponectin and alpha-glycoprotein. On the contrary, CDs with a lower zeta-potential (+11 mV) and charge density (0.01 mumol mg(-1)) are poorly internalized, while having a corona with a very different protein signature characterized by a high abundance of apolipoproteins (APOA1, APOB and APOC), albumin and hemoglobin. These data illustrate how corona characterization may contribute to a better understanding of CD cellular fate and biological effects, and provide useful information for the development of CDs for biomedical applications.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Beaussart2022b,

title = {Probing the mechanism of the peroxiredoxin decamer interaction with its reductase sulfiredoxin from the single molecule to the solution scale},

author = {A Beaussart and F Canonico and H Mazon and J Hidalgo and S Cianferani and H Le Cordier and A Kriznik and S Rahuel-Clermont},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35234779},

doi = {10.1039/d2nh00037g},

issn = {2055-6764 (Electronic) 2055-6756 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nanoscale Horiz},

volume = {7},

issue = {5},

pages = {515-525},

abstract = {Peroxiredoxins from the Prx1 subfamily (Prx) are highly regulated multifunctional proteins involved in oxidative stress response, redox signaling and cell protection. Prx is a homodimer that associates into a decamer. The monomer C-terminus plays intricate roles in Prx catalytic functions, decamer stability and interaction with its redox partner, the small reductase sulfiredoxin (Srx), that regulates the switching between Prx cellular functions. As only static structures of covalent Prx-Srx complexes have been reported, whether Srx binding dissociates the decameric assembly and how Prx subunit flexibility impacts complex formation are unknown. Here, we assessed the non-covalent interaction mechanism and dynamics in the solution of Saccharomyces cerevisiae Srx with the ten subunits of Prx Tsa1 at the decamer level via a combination of multiscale biophysical approaches including native mass spectrometry. We show that the ten subunits of the decamer can be saturated by ten Srx molecules and that the Tsa1 decamer in complex with Srx does not dissociate in solution. Furthermore, the binding events of atomic force microscopy (AFM) tip-grafted Srx molecules to Tsa1 individual subunits were relevant to the interactions between free molecules in solution. Combined with protein engineering and rapid kinetics, the observation of peculiar AFM force-distance signatures revealed that Tsa1 C-terminus flexibility controls Tsa1/Srx two-step binding and dynamics and determines the force-induced dissociation of Srx from each subunit of the decameric complex in a sequential or concerted mode. This combined approach from the solution to the single-molecule level offers promising prospects for understanding oligomeric protein interactions with their partners.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Awan2022b,

title = {Wnt5a Promotes Lysosomal Cholesterol Egress and Protects Against Atherosclerosis},

author = {S Awan and M Lambert and A Imtiaz and F Alpy and C Tomasetto and M Oulad-Abdelghani and C Schaeffer and C Moritz and D Julien-David and S Najib and L O Martinez and R L Matz and X Collet and R Silva-Rojas and J Bohm and J Herz and J Terrand and P Boucher},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34886684},

doi = {10.1161/CIRCRESAHA.121.318881},

issn = {1524-4571 (Electronic) 0009-7330 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Circ Res},

volume = {130},

issue = {2},

pages = {184-199},

abstract = {BACKGROUND: Impairment of cellular cholesterol trafficking is at the heart of atherosclerotic lesions formation. This involves egress of cholesterol from the lysosomes and 2 lysosomal proteins, the NPC1 (Niemann-Pick C1) and NPC2 that promotes cholesterol trafficking. However, movement of cholesterol out the lysosome and how disrupted cholesterol trafficking leads to atherosclerosis is unclear. As the Wnt ligand, Wnt5a inhibits the intracellular accumulation of cholesterol in multiple cell types, we tested whether Wnt5a interacts with the lysosomal cholesterol export machinery and studied its role in atherosclerotic lesions formation. METHODS: We generated mice deleted for the Wnt5a gene in vascular smooth muscle cells. To establish whether Wnt5a also protects against cholesterol accumulation in human vascular smooth muscle cells, we used a CRISPR/Cas9 guided nuclease approach to generate human vascular smooth muscle cells knockout for Wnt5a. RESULTS: We show that Wnt5a is a crucial component of the lysosomal cholesterol export machinery. By increasing lysosomal acid lipase expression, decreasing metabolic signaling by the mTORC1 (mechanistic target of rapamycin complex 1) kinase, and through binding to NPC1 and NPC2, Wnt5a senses changes in dietary cholesterol supply and promotes lysosomal cholesterol egress to the endoplasmic reticulum. Consequently, loss of Wnt5a decoupled mTORC1 from variations in lysosomal sterol levels, disrupted lysosomal function, decreased cholesterol content in the endoplasmic reticulum, and promoted atherosclerosis. CONCLUSIONS: These results reveal an unexpected function of the Wnt5a pathway as essential for maintaining cholesterol homeostasis in vivo.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Beinsteiner2022b,

title = {A novel nuclear receptor subfamily enlightens the origin of heterodimerization},

author = {B Beinsteiner and G V Markov and M Bourguet and A G McEwen and S Erb and A K M Patel and F Z El Khaloufi El Khaddar and C Lecroisey and G Holzer and K Essabri and I Hazemann and A Hamiche and S Cianferani and D Moras and V Laudet and I M L Billas},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36199108},

doi = {10.1186/s12915-022-01413-0},

issn = {1741-7007 (Electronic) 1741-7007 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {BMC Biol},

volume = {20},

issue = {1},

pages = {217},

abstract = {BACKGROUND: Nuclear receptors are transcription factors of central importance in human biology and associated diseases. Much of the knowledge related to their major functions, such as ligand and DNA binding or dimerization, derives from functional studies undertaken in classical model animals. It has become evident, however, that a deeper understanding of these molecular functions requires uncovering how these characteristics originated and diversified during evolution, by looking at more species. In particular, the comprehension of how dimerization evolved from ancestral homodimers to a more sophisticated state of heterodimers has been missing, due to a too narrow phylogenetic sampling. Here, we experimentally and phylogenetically define the evolutionary trajectory of nuclear receptor dimerization by analyzing a novel NR7 subgroup, present in various metazoan groups, including cnidarians, annelids, mollusks, sea urchins, and amphioxus, but lost in vertebrates, arthropods, and nematodes. RESULTS: We focused on NR7 of the cephalochordate amphioxus B. lanceolatum. We present a complementary set of functional, structural, and evolutionary analyses that establish that NR7 lies at a pivotal point in the evolutionary trajectory from homodimerizing to heterodimerizing nuclear receptors. The crystal structure of the NR7 ligand-binding domain suggests that the isolated domain is not capable of dimerizing with the ubiquitous dimerization partner RXR. In contrast, the full-length NR7 dimerizes with RXR in a DNA-dependent manner and acts as a constitutively active receptor. The phylogenetic and sequence analyses position NR7 at a pivotal point, just between the basal class I nuclear receptors that form monomers or homodimers on DNA and the derived class II nuclear receptors that exhibit the classical DNA-independent RXR heterodimers. CONCLUSIONS: Our data suggest that NR7 represents the "missing link" in the transition between class I and class II nuclear receptors and that the DNA independency of heterodimer formation is a feature that was acquired during evolution. Our studies define a novel paradigm of nuclear receptor dimerization that evolved from DNA-dependent to DNA-independent requirements. This new concept emphasizes the importance of DNA in the dimerization of nuclear receptors, such as the glucocorticoid receptor and other members of this pharmacologically important oxosteroid receptor subfamily. Our studies further underline the importance of studying emerging model organisms for supporting cutting-edge research.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis},

author = {M Bobowski-Gerard and C Boulet and F P Zummo and J Dubois-Chevalier and C Gheeraert and M Bou Saleh and J M Strub and A Farce and M Ploton and L Guille and J Vandel and A Bongiovanni and N Very and E Woitrain and A Deprince and F Lalloyer and E Bauge and L Ferri and L C Ntandja-Wandji and A K Cotte and C Grangette and E Vallez and S Cianferani and V Raverdy and R Caiazzo and V Gnemmi and E Leteurtre and B Pourcet and R Paumelle and K Ravnskjaer and G Lassailly and J T Haas and P Mathurin and F Pattou and L Dubuquoy and B Staels and P Lefebvre and J Eeckhoute},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36088459},

doi = {10.1038/s41467-022-33063-9},

issn = {2041-1723 (Electronic) 2041-1723 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Nat Commun},

volume = {13},

issue = {1},

pages = {5324},

abstract = {Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analyses unraveling Basonuclin 2 (BNC2) as a myofibroblast identity transcription factor. Using liver fibrosis as a model for in-depth investigations, we first show that BNC2 expression is induced in both mouse and human fibrotic livers from different etiologies and decreases upon human liver fibrosis regression. Importantly, we found that BNC2 transcriptional induction is a specific feature of myofibroblastic activation in fibrotic tissues. Mechanistically, BNC2 expression and activities allow to integrate pro-fibrotic stimuli, including TGFbeta and Hippo/YAP1 signaling, towards induction of matrisome genes such as those encoding type I collagen. As a consequence, Bnc2 deficiency blunts collagen deposition in livers of mice fed a fibrogenic diet. Additionally, our work establishes BNC2 as potentially druggable since we identified the thalidomide derivative CC-885 as a BNC2 inhibitor. Altogether, we propose that BNC2 is a transcription factor involved in canonical pathways driving myofibroblastic activation in fibrosis.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Boutin2022b,

title = {Measuring the NQO2: Melatonin Complex by Native Nano-Electrospray Ionization Mass Spectrometry},

author = {J A Boutin and J Stojko and G Ferry and S Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36180703},

doi = {10.1007/978-1-0716-2593-4_34},

issn = {1940-6029 (Electronic) 1064-3745 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Methods Mol Biol},

volume = {2550},

pages = {323-328},

abstract = {Melatonin exerts its effects through a series of target proteins/receptors and enzymes. Its antioxidant capacity might be due to its capacity to inhibit a quinone reductase (NQO2) at high concentration (50 muM). Demonstrating the existence of a complex between a compound and a protein is often not easy. It requires either that the compound is an inhibitor-and the complex translates by an inhibition of the catalytic activity-or the compound is radiolabeled-and the complex translates in standard binding approaches, such as in receptology. Outside these two cases, the detection of the protein:small molecule complexes by mass spectrometry has recently been made possible, thanks to the development of so-called native mass spectrometry. Using this approach, one can measure masses corresponding to an intact noncovalent complex between a compound and its target, usually after titration or competition experiments. In the present chapter, we detail the characterization of NQO2:melatonin interaction using native mass spectrometry.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Brun2022b,

title = {Resistance to glycation in the zebra finch: Mass spectrometry-based analysis and its perspectives for evolutionary studies of aging},

author = {C Brun and O Hernandez-Alba and A Hovasse and F Criscuolo and C Schaeffer-Reiss and F Bertile},

url = {<Go to ISI>://WOS:000799037700003},

doi = {ARTN 111811 10.1016/j.exger.2022.111811},

issn = {0531-5565},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Experimental Gerontology},

volume = {164},

abstract = {In humans, hyperglycemia is associated with protein glycation, which may contribute to aging. Strikingly, birds usually outlive mammals of the same body mass, while exhibiting high plasma glucose levels. However, how birds succeed in escaping pro-aging effects of glycation remains unknown. Using a specific mass spectrometrybased approach in captive zebra finches of known age, we recorded high glycaemia values but no glycated hemoglobin form was found. Still, we showed that zebra finch hemoglobin can be glycated in vitro, albeit only to a limited extent compared to its human homologue. This may be due to peculiar structural features, as supported by the unusual presence of three different tetramer populations with balanced proportions and a still bound cofactor that could be inositol pentaphosphate. High levels of the glycated forms of zebra finch plasma serotransferrin, carbonic anhydrase 2, and albumin were measured. Glucose, age or body mass correlations with either plasma glycated proteins or hemoglobin isoforms suggest that those variables may be future molecular tools of choice to monitor glycation and its link with individual fitness. Our molecular advance may help determine how evolution succeeded in associating flying ability, high blood glucose and long lifespan in birds.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cavazza2022b,

title = {Proteomic analysis of Rhodospirillum rubrum after carbon monoxide exposure reveals an important effect on metallic cofactor biosynthesis},

author = {C Cavazza and V Collin-Faure and J Perard and H Diemer and S Cianferani and T Rabilloud and E Darrouzet},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34601154},

doi = {10.1016/j.jprot.2021.104389},

issn = {1876-7737 (Electronic) 1874-3919 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {J Proteomics},

volume = {250},

pages = {104389},

abstract = {Some carboxydotrophs like Rhodospirillum rubrum are able to grow with CO as their sole source of energy using a Carbone monoxide dehydrogenase (CODH) and an Energy conserving hydrogenase (ECH) to perform anaerobically the so called water-gas shift reaction (WGSR) (CO + H2O – CO2 + H2). Several studies have focused at the biochemical and biophysical level on this enzymatic system and a few OMICS studies on CO metabolism. Knowing that CO is toxic in particular due to its binding to heme iron atoms, and is even considered as a potential antibacterial agent, we decided to use a proteomic approach in order to analyze R. rubrum adaptation in term of metabolism and management of the toxic effect. In particular, this study allowed highlighting a set of proteins likely implicated in ECH maturation, and important perturbations in term of cofactor biosynthesis, especially metallic cofactors. This shows that even this CO tolerant microorganism cannot avoid completely CO toxic effects associated with its interaction with metallic ions. SIGNIFICANCE: This proteomic study highlights the fact that even in a microorganism able to handle carbon monoxide and in some way detoxifying it via the intrinsic action of the carbon monoxide dehydrogenase (CODH), CO has important effects on metal homeostasis, metal cofactors and metalloproteins. These effects are direct or indirect via transcription regulation, and amplified by the high interdependency of cofactors biosynthesis.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chazarin2022b,

title = {Molecular Liver Fingerprint Reflects the Seasonal Physiology of the Grey Mouse Lemur (Microcebus murinus) during Winter},

author = {B Chazarin and M Benhaim-Delarbre and C Brun and A Anzeraey and F Bertile and J Terrien},

url = {<Go to ISI>://WOS:000785517200001},

doi = {ARTN 4254 10.3390/ijms23084254},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {International Journal of Molecular Sciences},

volume = {23},

issue = {8},

abstract = {Grey mouse lemurs (Microcebus murinus) are primates that respond to environmental energetic constraints through strong physiological seasonality. They notably fatten during early winter (EW), and mobilize their lipid reserves while developing glucose intolerance during late winter (LW), when food availability is low. To decipher how the hepatic mechanisms may support such metabolic flexibility, we analyzed the liver proteome of adult captive male mouse lemurs, whose seasonal regulations are comparable to their wild counterparts. We highlight profound hepatic changes that reflect fat accretion in EW at the whole-body level, without triggering an ectopic storage of fat in the liver, however. Moreover, molecular regulations are consistent with the decrease in liver glucose utilization in LW, and therefore with reduced tolerance to glucose. However, no major regulation was seen in insulin signaling/resistance pathways. Fat mobilization in LW appeared possibly linked to the reactivation of the reproductive system while enhanced liver detoxification may reflect an anticipation to return to summer levels of food intake. Overall, these results show that the physiology of mouse lemurs during winter relies on solid molecular foundations in liver processes to adapt fuel partitioning while opposing the development of a pathological state despite large lipid fluxes.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chion2022b,

title = {Accounting for multiple imputation-induced variability for differential analysis in mass spectrometry-based label-free quantitative proteomics},

author = {M Chion and C Carapito and F Bertrand},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36037245},

doi = {10.1371/journal.pcbi.1010420},

issn = {1553-7358 (Electronic) 1553-734X (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {PLoS Comput Biol},

volume = {18},

issue = {8},

pages = {e1010420},

abstract = {Imputing missing values is common practice in label-free quantitative proteomics. Imputation aims at replacing a missing value with a user-defined one. However, the imputation itself may not be optimally considered downstream of the imputation process, as imputed datasets are often considered as if they had always been complete. Hence, the uncertainty due to the imputation is not adequately taken into account. We provide a rigorous multiple imputation strategy, leading to a less biased estimation of the parameters' variability thanks to Rubin's rules. The imputation-based peptide's intensities' variance estimator is then moderated using Bayesian hierarchical models. This estimator is finally included in moderated t-test statistics to provide differential analyses results. This workflow can be used both at peptide and protein-level in quantification datasets. Indeed, an aggregation step is included for protein-level results based on peptide-level quantification data. Our methodology, named mi4p, was compared to the state-of-the-art limma workflow implemented in the DAPAR R package, both on simulated and real datasets. We observed a trade-off between sensitivity and specificity, while the overall performance of mi4p outperforms DAPAR in terms of F-Score.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Does size matter? A proteomics-informed comparison of the effects of polystyrene beads of different sizes on macrophages},

author = {V Collin-Faure and B Dalzon and J Devcic and H Diemer and S Cianferani and T Rabilloud},

url = {<Go to ISI>://WOS:000820824900001},

doi = {10.1039/d2en00214k},

issn = {2051-8153},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Environmental Science-Nano},

volume = {9},

issue = {8},

pages = {2827-2840},

abstract = {Plastics are one of the most preoccupying emerging pollutants. Macroplastics released into the environment degrade into microplastics and nanoplastics. Because of their small size, these micro and nano plastic particles can enter the food chain and, in addition to their ecotoxicological effects, contaminate humans with still unknown biological effects. Plastics being particulate pollutants, they are handled in the human body by scavenger cells such as macrophages, which are important players in the immune system. In order to get a better appraisal of the effects of plastic particles on macrophages, we have studied the effects of unmodified polystyrene particles of 0.1, 1 and 10 micrometers of diameter, by a combination of proteomics and targeted validation experiments. Proteomics showed important adaptive changes of the proteome in response to exposure to plastics, with more than one third of the detected proteins showing a significance change in their abundance in response to cell exposure to at least one plastic bead size. These changes affected for example mitochondrial, lysosomal or cytoskeletal proteins. Although an increase in the mitochondrial transmembrane potential was detected in response to 10 micrometer beads, no alteration in cell viability was observed. Similarly, no lysosomal dysfunction and no alteration in the phagocytic capability of the cells was observed in response to exposure to plastics. When the inflammatory response was examined, no increase in the secretion of tumor necrosis factor or interleukin 6 was observed. Oppositely, the secretion of these cytokines in response to lipopolysaccharide was observed after exposure to plastics, which suggested a decreased ability of macrophages to respond to bacterial infection. In conclusion, these results provide a better understanding of the responses of macrophages to exposure to polystyrene particles of different sizes.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cotin2022b,

title = {A Confinement-Driven Nucleation Mechanism of Metal Oxide Nanoparticles Obtained via Thermal Decomposition in Organic Media},

author = {G Cotin and B Heinrich and F Perton and C Kiefer and G Francius and D Mertz and B Freis and B Pichon and J M Strub and S Cianferani and N Ortiz Pena and D Ihiawakrim and D Portehault and O Ersen and A Khammari and M Picher and F Banhart and C Sanchez and S Begin-Colin},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35426247},

doi = {10.1002/smll.202200414},

issn = {1613-6829 (Electronic) 1613-6810 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Small},

volume = {18},

issue = {20},

pages = {e2200414},

abstract = {Thermal decomposition is a very efficient synthesis strategy to obtain nanosized metal oxides with controlled structures and properties. For the iron oxide nanoparticle synthesis, it allows an easy tuning of the nanoparticle's size, shape, and composition, which is often explained by the LaMer theory involving a clear separation between nucleation and growth steps. Here, the events before the nucleation of iron oxide nanocrystals are investigated by combining different complementary in situ characterization techniques. These characterizations are carried out not only on powdered iron stearate precursors but also on a preheated liquid reaction mixture. They reveal a new nucleation mechanism for the thermal decomposition method: instead of a homogeneous nucleation, the nucleation occurs within vesicle-like-nanoreactors confining the reactants. The different steps are: 1) the melting and coalescence of iron stearate particles, leading to "droplet-shaped nanostructures" acting as nanoreactors; 2) the formation of a hitherto unobserved iron stearate crystalline phase within the nucleation temperature range, simultaneously with stearate chains loss and Fe(III) to Fe(II) reduction; 3) the formation of iron oxide nuclei inside the nanoreactors, which are then ejected from them. This mechanism paves the way toward a better mastering of the metal oxide nanoparticles synthesis and the control of their properties.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Colome2022d,

title = {Multi-laboratory experiment PME11 for the standardization of phosphoproteome analysis},

author = {N Colome and J Abian and K Aloria and J M Arizmendi and S Barcelo-Batllori and S Braga-Lagache and O Burlet-Schiltz and M Carrascal and J I Casal and E Chicano-Galvez and C Chiva and L F Clemente and F Elortza and J M Estanyol and J Fernandez-Irigoyen and P Fernandez-Puente and M J Fidalgo and C Froment and M Fuentes and C Fuentes-Almagro and M Gay and A Hainard and M Heller and M L Hernandez and N Ibarrola and I Iloro and T Kieselbach and A Lario and M Locard-Paulet and A Marina-Ramirez and L Martin and E Morato-Lopez and J Munoz and R Navajas and M A Odena and L Odriozola and E Oliveira and A Paradela and C Pasquarello and V Los Rios and C Ruiz-Romero and E Sabido and M Sanchez Del Pino and J Sancho and E Santamaria and C Schaeffer-Reiss and J Schneider and C Torre and M L Valero and M Vilaseca and S Wu and L Wu and P Embun and F Canals and F J Corrales and Isciii ProteoRed and EuPa},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34758407},

doi = {10.1016/j.jprot.2021.104409},

issn = {1876-7737 (Electronic) 1874-3919 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {J Proteomics},

volume = {251},

pages = {104409},

abstract = {Global analysis of protein phosphorylation by mass spectrometry proteomic techniques has emerged in the last decades as a powerful tool in biological and biomedical research. However, there are several factors that make the global study of the phosphoproteome more challenging than measuring non-modified proteins. The low stoichiometry of the phosphorylated species and the need to retrieve residue specific information require particular attention on sample preparation, data acquisition and processing to ensure reproducibility, qualitative and quantitative robustness and ample phosphoproteome coverage in phosphoproteomic workflows. Aiming to investigate the effect of different variables in the performance of proteome wide phosphoprotein analysis protocols, ProteoRed-ISCIII and EuPA launched the Proteomics Multicentric Experiment 11 (PME11). A reference sample consisting of a yeast protein extract spiked in with different amounts of a phosphomix standard (Sigma/Merck) was distributed to 31 laboratories around the globe. Thirty-six datasets from 23 laboratories were analyzed. Our results indicate the suitability of the PME11 reference sample to benchmark and optimize phosphoproteomics strategies, weighing the influence of different factors, as well as to rank intra and inter laboratory performance.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Darriere2022b,

title = {Upon heat stress processing of ribosomal RNA precursors into mature rRNAs is compromised after cleavage at primary P site in Arabidopsis thaliana},

author = {T Darriere and E Jobet and D Zavala and M L Escande and N Durut and A Bures and F Blanco-Herrera and E A Vidal and M Rompais and C Carapito and S Gourbiere and J Saez-Vasquez},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35522061},

doi = {10.1080/15476286.2022.2071517},

issn = {1555-8584 (Electronic) 1547-6286 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {RNA Biol},

volume = {19},

issue = {1},

pages = {719-734},

abstract = {Transcription and processing of 45S rRNAs in the nucleolus are keystones of ribosome biogenesis. While these processes are severely impacted by stress conditions in multiple species, primarily upon heat exposure, we lack information about the molecular mechanisms allowing sessile organisms without a temperature-control system, like plants, to cope with such circumstances. We show that heat stress disturbs nucleolar structure, inhibits pre-rRNA processing and provokes imbalanced ribosome profiles in Arabidopsis thaliana plants. Notably, the accuracy of transcription initiation and cleavage at the primary P site in the 5'ETS (5' External Transcribed Spacer) are not affected but the levels of primary 45S and 35S transcripts are, respectively, increased and reduced. In contrast, precursors of 18S, 5.8S and 25S RNAs are rapidly undetectable upon heat stress. Remarkably, nucleolar structure, pre-rRNAs from major ITS1 processing pathway and ribosome profiles are restored after returning to optimal conditions, shedding light on the extreme plasticity of nucleolar functions in plant cells. Further genetic and molecular analysis to identify molecular clues implicated in these nucleolar responses indicate that cleavage rate at P site and nucleolin protein expression can act as a checkpoint control towards a productive pre-rRNA processing pathway.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Declercq2022b,

title = {MS(2)Rescore: Data-driven rescoring dramatically boosts immunopeptide identification rates},

author = {A Declercq and R Bouwmeester and A Hirschler and C Carapito and S Degroeve and L Martens and R Gabriels},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35803561},

doi = {10.1016/j.mcpro.2022.100266},

issn = {1535-9484 (Electronic) 1535-9476 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Mol Cell Proteomics},

pages = {100266},

abstract = {Immunopeptidomics aims to identify Major Histocompatibility Complex-presented peptides on almost all cell that can be used in anti-cancer vaccine development. However, existing immunopeptidomics data analysis pipelines suffer from the non-tryptic nature of immunopeptides, complicating their identification. Previously, peak intensity predictions by MS(2)PIP and retention time predictions by DeepLC, have been shown to improve tryptic peptide identifications when rescoring peptide-spectrum matches with Percolator. However, as MS(2)PIP was tailored towards tryptic peptides, we have here retrained MS(2)PIP to include non-tryptic peptides. Interestingly, the new models not only greatly improve predictions for immunopeptides, but also yield further improvements for tryptic peptides. We show that the integration of new MS(2)PIP models, DeepLC, and Percolator in one software package, MS(2)Rescore, increases spectrum identification rate and unique identified peptides with 46% and 36% compared to standard Percolator rescoring at 1% FDR. Moreover, MS(2)Rescore also outperforms the current state-of-the-art in immunopeptide-specific identification approaches. Altogether, MS(2)Rescore thus allows substantially improved identification of novel epitopes from existing immunopeptidomics workflows.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Desligniere2022d,

title = {A Combination of Native LC-MS Approaches for the Comprehensive Characterization of the Antibody-Drug Conjugate Trastuzumab Deruxtecan},

author = {E Desligniere and H Diemer and S Erb and P Coliat and X Pivot and A Detappe and O Hernandez-Alba and S Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36336868},

doi = {10.31083/j.fbl2710290},

issn = {2768-6698 (Electronic) 2768-6698 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Front Biosci (Landmark Ed)},

volume = {27},

issue = {10},

pages = {290},

abstract = {BACKGROUND: Native mass spectrometry (nMS) approaches appear attractive to complement bottom-up strategies traditionally used in biopharmaceutical industries thanks to their quite straightforward and rapid workflows, especially through online hyphenation of non-denaturing liquid chromatography (LC) to nMS. The present work provides an overview of the state-of-the-art chromatographic tools available for the detailed characterization of monoclonal antibody (mAb) formats, exemplified on the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd). METHODS: T-DXd was first characterized by conventional reversed phase LC (rpLC) and peptide mapping. Couplings of size exclusion chromatography (SEC), cation exchange chromatography (CEX), and hydrophobic interaction chromatography (HIC) to nMS were used to gain further insights into size, hydrophobic, and charge variants of T-DXd and its parental mAb trastuzumab, at intact and middle-up levels. RESULTS: SEC-nMS first offered a direct snapshot of the homogeneous conjugation of T-DXd, with an average drug-to-antibody ratio (DAR) of 8 in agreement with a conjugation on cysteines after reduction of all interchain disulfide bonds. Moreover, SEC-nMS afforded precise identification and quantification of aggregates and fragments. Middle-up level experiments performed after IdeS digestion confirmed that drug conjugation occurs in the Fab region of the mAb, as seen with rpLC. HIC separated two DAR8 species that could not be differentiated by nMS. Although middle-up HIC-nMS proved to be more informative for oxidized forms, the identification of minor variants was still difficult because of poor MS signal quality, showing how the coupling of HIC to nMS remains challenging. Lastly, middle-up CEX-nMS provided accurate determination and localization of post-translational modifications, with several acidic/basic variants within Fab and Fc regions of T-DXd that were also identified by peptide mapping. CONCLUSIONS: This study illustrates the strengths and drawbacks of each LC-nMS coupling. By combining SEC-, HIC-, and CEX-nMS, we were able to achieve a comprehensive characterization of T-DXd without extensive sample preparation prior to MS analysis.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Advanced IM-MS-based Approaches for Protein Analysis: Collision-induced Unfolding (CIU) and Hyphenation of Liquid Chromatography to IM-MS},

author = {E Deslignière and O Hernandez-Alba and S Cianférani},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {in New developemnts in MS : ion -mobility Mass Spectrometry},

volume = {chapter 16},

pages = {436-460},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Desligniere2022c,

title = {Combination of IM-Based Approaches to Unravel the Coexistence of Two Conformers on a Therapeutic Multispecific mAb},

author = {E Desligniere and S Ollivier and A Ehkirch and A Martelet and D Ropartz and N Lechat and O Hernandez-Alba and J M Menet and S Clavier and H Rogniaux and B Genet and S Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35604400},

doi = {10.1021/acs.analchem.2c00928},

issn = {1520-6882 (Electronic) 0003-2700 (Linking)},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Anal Chem},

volume = {94},

issue = {22},

pages = {7981-7989},

abstract = {Multispecific antibodies, which target multiple antigens at once, are emerging as promising therapeutic entities to offer more effective treatment than conventional monoclonal antibodies (mAbs). However, these highly complex mAb formats pose significant analytical challenges. We report here on the characterization of a trispecific antibody (tsAb), which presents two isomeric forms clearly separated and identified with size exclusion chromatography coupled to native mass spectrometry (SEC-nMS). Previous studies showed that these isomers might originate from a proline cis/trans isomerization in one Fab subunit of the tsAb. We combined several innovative ion mobility (IM)-based approaches to confirm the isomeric nature of the two species and to gain new insights into the conformational landscape of both isomers. Preliminary SEC-nIM-MS measurements performed on a low IM resolution instrument provided the first hints of the coexistence of different conformers, while complementary collision-induced unfolding (CIU) experiments evidenced distinct gas-phase unfolding behaviors upon activation for the two isomers. As subtle conformational differences remained poorly resolved on our early generation IM platform, we performed high-resolution cyclic IM (cIM-MS) to unambiguously conclude on the coexistence of two conformers. The cis/trans equilibrium was further tackled by exploiting the IM(n) slicing capabilities of the cIM-MS instrument. Altogether, our results clearly illustrate the benefits of combining state-of-the-art nMS and IM-MS approaches to address challenging issues encountered in biopharma. As engineered antibody constructs become increasingly sophisticated, CIU and cIM-MS methodologies undoubtedly have the potential to integrate the drug development analytical toolbox to achieve in-depth conformational characterization of these products.},

note = {Type: Journal Article},

keywords = {},

pubstate = {published},

tppubtype = {article}

}