@article{RN1907,

title = {Targeted delivery of immune-stimulating bispecific RNA, inducing apoptosis and anti-tumor immunity in cancer cells},

author = {T. Rady and S. Erb and S. Deddouche-Grass and R. Morales and G. Chaubet and S. Cianférani and N. Basse and A. Wagner},

url = {<Go to ISI>://WOS:001188408500001},

doi = {ARTN 109068 

10.1016/j.isci.2024.109068},

year  = {2024},

date = {2024-01-01},

journal = {Iscience},

volume = {27},

number = {3},

abstract = {Double -stranded RNAs (dsRNA)-based strategies appeared as promising therapies to induce an inflammation in the tumor microenvironment. However, currently described systems generally lack active targeting of tissues, and their clinical translation is thus limited to intratumoral injection. Herein, we developed an antibody-siRNA-50triphosphate conjugate with multiple modes of action, combining cell surface EphA2-specific internalization, leading to a simultaneous gene silencing and activation of the receptor retinoic acid -inducible gene I (RIG -I). Recognition of cytosolic siRNA-50triphosphate by RIG -I triggers the expression of interferons and pro -inflammatory cytokines, inducing an inflammation of the tumor environment and activating neighboring immune cells. In addition, these RIG -I -specific effects synergized with siRNA-mediated PLK1 silencing to promote cancer cell death by apoptosis. Altogether, such immune -stimulating antibody -RNA conjugate opens a novel modality to overcome some limitations encountered by dsRNA molecules currently in clinical trials.},

note = {Lr0j5 

Times Cited:0 

Cited References Count:48},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1916,

title = {Brain exposure to SARS-CoV-2 virions perturbs synaptic homeostasis},

author = {E. Partiot and A. Hirschler and S. Colomb and W. Lutz and T. Claeys and F. Delalande and M. S. Deffieu and Y. Bare and J. R. E. Roels and B. Gorda and J. Bons and D. Callon and L. Andreoletti and M. Labrousse and F. M. J. Jacobs and V. Rigau and B. Charlot and L. Martens and C. Carapito and G. Ganesh and R. Gaudin},

url = {<Go to ISI>://WOS:001194694400001},

doi = {10.1038/s41564-024-01657-2},

issn = {2058-5276},

year  = {2024},

date = {2024-01-01},

journal = {Nature Microbiology},

abstract = {Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with short- and long-term neurological complications. The variety of symptoms makes it difficult to unravel molecular mechanisms underlying neurological sequalae after coronavirus disease 2019 (COVID-19). Here we show that SARS-CoV-2 triggers the up-regulation of synaptic components and perturbs local electrical field potential. Using cerebral organoids, organotypic culture of human brain explants from individuals without COVID-19 and post-mortem brain samples from individuals with COVID-19, we find that neural cells are permissive to SARS-CoV-2 to a low extent. SARS-CoV-2 induces aberrant presynaptic morphology and increases expression of the synaptic components Bassoon, latrophilin-3 (LPHN3) and fibronectin leucine-rich transmembrane protein-3 (FLRT3). Furthermore, we find that LPHN3-agonist treatment with Stachel partially restored organoid electrical activity and reverted SARS-CoV-2-induced aberrant presynaptic morphology. Finally, we observe accumulation of relatively static virions at LPHN3-FLRT3 synapses, suggesting that local hindrance can contribute to synaptic perturbations. Together, our study provides molecular insights into SARS-CoV-2-brain interactions, which may contribute to COVID-19-related neurological disorders. 

Exposing cerebral organoids and post-mortem brain explants to SARS-CoV-2 virus particles alters expression of synaptic proteins and potentially affects synaptic function by blocking LPHN3 and FLRT3 synapses.},

note = {Mo9z3 

Times Cited:0 

Cited References Count:72},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1915,

title = {Regulations of mitoNEET by the key redox homeostasis molecule glutathione},

author = {C. Mons and M. Salameh and T. Botzanowski and M. Clemancey and P. Dorlet and C. Vallieres and S. Erb and L. Vernis and O. Guittet and M. Lepoivre and M. E. Huang and S. Cianferani and J. M. Latour and G. Blondin and M. P. Golinelli-Cohen},

url = {https://www.ncbi.nlm.nih.gov/pubmed/38527404 

https://www.sciencedirect.com/science/article/pii/S0162013424000588?via%3Dihub},

doi = {10.1016/j.jinorgbio.2024.112535},

issn = {1873-3344 (Electronic) 

0162-0134 (Linking)},

year  = {2024},

date = {2024-01-01},

journal = {J Inorg Biochem},

volume = {255},

pages = {112535},

abstract = {Human mitoNEET (mNT) and CISD2 are two NEET proteins characterized by an atypical [2Fe-2S] cluster coordination involving three cysteines and one histidine. They act as redox switches with an active state linked to the oxidation of their cluster. In the present study, we show that reduced glutathione but also free thiol-containing molecules such as beta-mercaptoethanol can induce a loss of the mNT cluster under aerobic conditions, while CISD2 cluster appears more resistant. This disassembly occurs through a radical-based mechanism as previously observed with the bacterial SoxR. Interestingly, adding cysteine prevents glutathione-induced cluster loss. At low pH, glutathione can bind mNT in the vicinity of the cluster. These results suggest a potential new regulation mechanism of mNT activity by glutathione, an essential actor of the intracellular redox state.},

note = {Mons, Cecile 

Salameh, Myriam 

Botzanowski, Thomas 

Clemancey, Martin 

Dorlet, Pierre 

Vallieres, Cindy 

Erb, Stephane 

Vernis, Laurence 

Guittet, Olivier 

Lepoivre, Michel 

Huang, Meng-Er 

Cianferani, Sarah 

Latour, Jean-Marc 

Blondin, Genevieve 

Golinelli-Cohen, Marie-Pierre 

eng 

2024/03/26 

J Inorg Biochem. 2024 Jun;255:112535. doi: 10.1016/j.jinorgbio.2024.112535. Epub 2024 Mar 20.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1917,

title = {Thunder-DDA-PASEF enables high-coverage immunopeptidomics and is boosted by MS(2)Rescore with MS(2)PIP timsTOF fragmentation prediction model},

author = {D. Gomez-Zepeda and D. Arnold-Schild and J. Beyrle and A. Declercq and R. Gabriels and E. Kumm and A. Preikschat and M. K. Lacki and A. Hirschler and J. B. Rijal and C. Carapito and L. Martens and U. Distler and H. Schild and S. Tenzer},

url = {https://www.ncbi.nlm.nih.gov/pubmed/38480730},

doi = {10.1038/s41467-024-46380-y},

issn = {2041-1723 (Electronic) 

2041-1723 (Linking)},

year  = {2024},

date = {2024-01-01},

journal = {Nat Commun},

volume = {15},

number = {1},

pages = {2288},

abstract = {Human leukocyte antigen (HLA) class I peptide ligands (HLAIps) are key targets for developing vaccines and immunotherapies against infectious pathogens or cancer cells. Identifying HLAIps is challenging due to their high diversity, low abundance, and patient individuality. Here, we develop a highly sensitive method for identifying HLAIps using liquid chromatography-ion mobility-tandem mass spectrometry (LC-IMS-MS/MS). In addition, we train a timsTOF-specific peak intensity MS(2)PIP model for tryptic and non-tryptic peptides and implement it in MS(2)Rescore (v3) together with the CCS predictor from ionmob. The optimized method, Thunder-DDA-PASEF, semi-selectively fragments singly and multiply charged HLAIps based on their IMS and m/z. Moreover, the method employs the high sensitivity mode and extended IMS resolution with fewer MS/MS frames (300 ms TIMS ramp, 3 MS/MS frames), doubling the coverage of immunopeptidomics analyses, compared to the proteomics-tailored DDA-PASEF (100 ms TIMS ramp, 10 MS/MS frames). Additionally, rescoring boosts the HLAIps identification by 41.7% to 33%, resulting in 5738 HLAIps from as little as one million JY cell equivalents, and 14,516 HLAIps from 20 million. This enables in-depth profiling of HLAIps from diverse human cell lines and human plasma. Finally, profiling JY and Raji cells transfected to express the SARS-CoV-2 spike protein results in 16 spike HLAIps, thirteen of which have been reported to elicit immune responses in human patients.},

note = {Gomez-Zepeda, David 

Arnold-Schild, Danielle 

Beyrle, Julian 

Declercq, Arthur 

Gabriels, Ralf 

Kumm, Elena 

Preikschat, Annica 

Lacki, Mateusz Krzysztof 

Hirschler, Aurelie 

Rijal, Jeewan Babu 

Carapito, Christine 

Martens, Lennart 

Distler, Ute 

Schild, Hansjorg 

Tenzer, Stefan 

eng 

England 

2024/03/14 

Nat Commun. 2024 Mar 13;15(1):2288. doi: 10.1038/s41467-024-46380-y.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1918,

title = {Ionic Liquid Crystals Based on Loop-Shaped Copper(I) Complexes},

author = {N. Del Giudice and G. Voegeli and J. M. Strub and B. Heinrich and L. Douce},

url = {https://www.ncbi.nlm.nih.gov/pubmed/38497643},

doi = {10.1021/acs.inorgchem.4c00728},

issn = {1520-510X (Electronic) 

0020-1669 (Linking)},

year  = {2024},

date = {2024-01-01},

journal = {Inorg Chem},

volume = {63},

number = {13},

pages = {6103-6110},

abstract = {This paper describes the synthesis and characterization of liquid crystals based on loop-shaped cationic copper(I) complexes of a multidentate ligand. Their synthesis involves the one-pot reaction of an alkyloxy-decorated pyridine-aldehyde unit with a diamine (2,2'-(ethylenedioxy)bis(ethylamine)) spacer to form in situ a pyridine-imine quadridentate-N(4)-donor ligand, L, which is able to chelate a copper(I) center associated with various noncoordinating anions. All of these compounds were characterized by NMR, IR, and electronic absorption spectroscopy, and more particularly by X-ray diffraction and mass spectroscopy, enabling unambiguous assignment of the [ML](+) mononuclear nature of the cationic components. The presence of six flexible alkyloxy chains at each end of the ligand associated with the rigidity of the core complex causes induction of a liquid crystal state with a columnar self-organized architecture, where the columns are packed in a hexagonal two-dimensional network.},

note = {Del Giudice, Nicolas 

Voegeli, Guillaume 

Strub, Jean-Marc 

Heinrich, Benoit 

Douce, Laurent 

eng 

2024/03/18 

Inorg Chem. 2024 Apr 1;63(13):6103-6110. doi: 10.1021/acs.inorgchem.4c00728. Epub 2024 Mar 18.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1908,

title = {SEC-MS in denaturing conditions (dSEC-MS) for in-depth analysis of rebridged monoclonal antibody-based formats},

author = {R. Benazza and I. Koutsopetras and V. Vaur and G. Chaubet and O. H. -. Alba and S. Cianferani},

url = {<Go to ISI>://WOS:001188643100001},

doi = {ARTN 125727 

10.1016/j.talanta.2024.125727},

issn = {0039-9140},

year  = {2024},

date = {2024-01-01},

journal = {Talanta},

volume = {272},

abstract = {Disulfide rebridging methods are emerging recently as new ways to specifically modify antibody -based entities and produce future conjugates. Briefly, the solvent -accessible disulfide bonds of antibodies or antigen -binding fragments (Fab) thereof are reduced under controlled conditions and further covalently attached with a rebridging agent allowing the incorporation of one payload per disulfide bond. There are many examples of successful rebridging cases providing homogeneous conjugates due to the use of symmetrical reagents, such as dibromomaleimides. However, partial rebridging due to the use of unsymmetrical ones, containing functional groups with different reactivity, usually leads to the development of heterogeneous species that cannot be identified by a simple sodium dodecyl sulfate-polyacrylamide gel eletrophoresis (SDS-PAGE) due to its lack of sensitivity, resolution and low mass accuracy. Mass spectrometry coupled to liquid chromatography (LC -MS) approaches have already been demonstrated as highly promising alternatives for the characterization of newly developed antibody -drug -conjugate (ADC) and monoclonal antibody (mAb)-based formats. We report here the in-depth characterization of covalently rebridged antibodies and Fab fragments in -development, using sizeexclusion chromatography hyphenated to mass spectrometry in denaturing conditions (denaturing SEC -MS, dSEC-MS). DSEC-MS was used to monitor closely the rebridging reaction of a conjugated trastuzumab, in addition to conjugated Fab fragments, which allowed an unambiguous identification of the covalently rebridged products along with the unbound species. This all -in -one approach allowed a straightforward analysis of the studied samples with precise mass measurement; critical quality attributes (CQAs) assessment along with rebridging efficiency determination.},

note = {Lr9i3 

Times Cited:0 

Cited References Count:0},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1911,

title = {Solution and Solvent-Free Stopper Exchange Reactions for the Preparation of Pillar[5]arene-containing [2] and [3]Rotaxanes},

author = {N. Becharguia and I. Nierengarten and J. M. Strub and S. Cianférani and M. Rémy and E. Wasielewski and R. Abidi and J. F. Nierengarten},

url = {<Go to ISI>://WOS:001143274700001},

doi = {10.1002/chem.202304131},

issn = {0947-6539},

year  = {2024},

date = {2024-01-01},

journal = {Chemistry-a European Journal},

volume = {30},

number = {12},

abstract = {Diamine reagents have been used to functionalize a [2]rotaxane building block bearing an activated pentafluorophenyl ester stopper. Upon a first acylation, an intermediate host-guest complex with a terminal amine function is obtained. Dissociation of the intermediate occurs in solution and acylation of the released axle generates a [2]rotaxane with an elongated axle subunit. In contrast, the corresponding [3]rotaxane can be obtained if the reaction conditions are appropriate to stabilize the inclusion complex of the mono-amine intermediate and the pillar[5]arene. This is the case when the stopper exchange is performed under mechanochemical solvent-free conditions. Alternatively, if the newly introduced terminal amide group is large enough to prevent the dissociation, the second acylation provides exclusively a [3]rotaxane. On the other hand, detailed conformational analysis has been also carried out by variable temperature NMR investigations. A complete understanding of the shuttling motions of the pillar[5]arene subunit along the axles of the rotaxanes reported therein has been achieved with the help of density functional theory calculations. 

Stopper exchange reactions between a rotaxane building block and diamine reagents gave dramatically different outcome in solution and in solvent-free conditions. Upon a first acylation, an intermediate host-guest complex with a terminal amine function is obtained. Dissociation of the intermediate occurs in solution but the inclusion complex is preserved under mechanochemical solvent-free conditions.image},

note = {Ka8n7 

Times Cited:0 

Cited References Count:74},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1921,

title = {Mesophotic zone as refuge: acclimation and in-depth proteomic response of yellow gorgonians in the Mediterranean sea},

author = {A. Beauvieux and B. Mérigot and J. Le Luyer and J. M. Fromentin and N. Couffin and A. Brown and O. Bianchimani and R. Hocdé and D. Aurelle and J. B. Ledoux and F. Bertile and Q. Schull},

url = {<Go to ISI>://WOS:001175315400001},

doi = {10.1007/s00338-024-02477-w},

issn = {0722-4028},

year  = {2024},

date = {2024-01-01},

journal = {Coral Reefs},

abstract = {The intensification of warming-induced mass-mortalities in invertebrate populations including in temperate regions is a critical global issue. Mesophotic zones (30-150 m depth) have been suggested as potential refuges from climate change for gorgonian populations, offering hope for reseeding damaged shallow populations. Using a proteomic approach, we investigated the responses and acclimatization ability of the yellow gorgonian Eunicella cavolini along an environmental gradient following reciprocal transplantations between shallow (20 m) and mesophotic (70 m) zones. Our findings indicate that yellow gorgonians from mesophotic waters exhibit a greater plasticity when transplanted to shallow waters, compared to shallow gorgonians transplanted to the mesophotic zone at 70 m. Transplanted colonies from mesophotic to shallow waters showed an increasing level of proteins involved in immune response but displayed no signs of necrosis or apoptosis, highlighting the acclimation potential of mesophotic populations. These results suggest that Eunicella cavolini populations may exhibit physiological plasticity in response to future climate change, allowing natural colonization from mesophotic populations. This analysis offers valuable insights into gorgonians' cellular and molecular responses to environmental changes.},

note = {Jt1f6 

Times Cited:0 

Cited References Count:69},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1920,

title = {Molecular fingerprint of gilthead seabream physiology in response to pollutant mixtures in the wild},

author = {A. Beauvieux and J. M. Fromentin and D. Romero and N. Couffin and A. Brown and L. Metral and J. Bourjea and F. Bertile and Q. Schull},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37913978},

doi = {10.1016/j.envpol.2023.122789},

issn = {1873-6424 (Electronic) 

0269-7491 (Linking)},

year  = {2024},

date = {2024-01-01},

journal = {Environ Pollut},

volume = {340},

number = {Pt 2},

pages = {122789},

abstract = {The increase in trace element concentrations in the aquatic environment due to anthropogenic activities, urges the need for their monitoring and potential toxicity, persistence, bioaccumulation, and biomagnification at different trophic levels. Gilthead seabream is a species of commercial importance in the Mediterranean Sea, both for the aquaculture and fisheries sectors, however very little is known about their trace element contamination accumulation and the resulting effect on their health status. In the present study, 135 juveniles were collected from seven coastal lagoons known to be essential nursery areas for this species. We measured seventeen different inorganic contaminants at the individual level in fish muscle (namely Al, As, Be, Bi, Cd, Cr, Cu, Hg, Li, Ni, Pb, Rb, Sb, Sr, Ti, Tl and Zn). Our results revealed the accumulation of multiple trace elements in individuals and distinct contamination signatures between lagoons which might lead to contrasted quality as nurseries for juveniles of numerous ecologically and economically relevant fish species in addition to seabreams. We further evaluated the potential adverse effect of these complex contamination mixtures on the liver (the main organ implicated in the metabolism of xenobiotics) and red muscle (a highly metabolic organ) using a proteomic approach. Alterations in cellular organization pathways and protein transport were detected in both tissues (albeit they were not similarly regulated). Chromosome organization and telomere maintenance in the liver appeared to be affected by contaminant mixture which could increase mortality, age-related disease risk and shorter lifetime expectancy for these juveniles. Red muscle proteome also demonstrated an upregulation of pathways involved in metabolism in response to contamination which raises the issue of potential energy allocation trade-offs between the organisms' main functions such as reproduction and growth. This study provides new insights into the cellular and molecular responses of seabreams to environmental pollution and proposed biomarkers of health effects of trace elements that could serve as a starting point for larger-scale biomonitoring programs.},

note = {Beauvieux, Anais 

Fromentin, Jean-Marc 

Romero, Diego 

Couffin, Nathan 

Brown, Adrien 

Metral, Luisa 

Bourjea, Jerome 

Bertile, Fabrice 

Schull, Quentin 

eng 

England 

2023/11/02 

Environ Pollut. 2024 Jan 1;340(Pt 2):122789. doi: 10.1016/j.envpol.2023.122789. Epub 2023 Oct 30.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1874,

title = {Online Collision-Induced Unfolding of Therapeutic Monoclonal Antibody Glyco-Variants through Direct Hyphenation of Cation Exchange Chromatography with Native Ion Mobility-Mass Spectrometry},

author = {G. Schaick and E. Dominguez-Vega and J. Castel and M. Wuhrer and O. Hernandez-Alba and S. Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36791123},

doi = {10.1021/acs.analchem.2c03163},

issn = {1520-6882 (Electronic) 

0003-2700 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Anal Chem},

volume = {95},

number = {8},

pages = {3932-3939},

abstract = {Post-translational modifications (PTMs) not only substantially increase structural heterogeneity of proteins but can also alter the conformation or even biological functions. Monitoring of these PTMs is particularly important for therapeutic products, including monoclonal antibodies (mAbs), since their efficacy and safety may depend on the PTM profile. Innovative analytical strategies should be developed to map these PTMs as well as explore possible induced conformational changes. Cation-exchange chromatography (CEX) coupled with native mass spectrometry has already emerged as a valuable asset for the characterization of mAb charge variants. Nevertheless, questions regarding protein conformation cannot be explored using this approach. Thus, we have combined CEX separation with collision-induced unfolding (CIU) experiments to monitor the unfolding pattern of separated mAbs and thereby pick up subtle conformational differences without impairing the CEX resolution. Using this novel strategy, only four CEX-CIU runs had to be recorded for a complete CIU fingerprint either at the intact mAb level or after enzymatic digestion at the mAb subunit level. As a proof of concept, CEX-CIU was first used for an isobaric mAb mixture to highlight the possibility to acquire individual CIU fingerprints of CEX-separated species without compromising CEX separation performances. CEX-CIU was next successfully applied to conformational characterization of mAb glyco-variants, in order to derive glycoform-specific information on the gas-phase unfolding, and CIU patterns of Fc fragments, revealing increased resistance of sialylated glycoforms against gas-phase unfolding. Altogether, we demonstrated the possibilities and benefits of combining CEX with CIU for in-depth characterization of mAb glycoforms, paving the way for linking conformational changes and resistance to gas-phase unfolding charge variants.},

note = {van Schaick, Guusje 

Dominguez-Vega, Elena 

Castel, Jerome 

Wuhrer, Manfred 

Hernandez-Alba, Oscar 

Cianferani, Sarah 

eng 

Research Support, Non-U.S. Gov't 

2023/02/16 06:00 

Anal Chem. 2023 Feb 28;95(8):3932-3939. doi: 10.1021/acs.analchem.2c03163. Epub 2023 Feb 15.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1883,

title = {Targeted Anticancer Agent with Original Mode of Action Prepared by Supramolecular Assembly of Antibody Oligonucleotide Conjugates and Cationic Nanoparticles},

author = {V. Lehot and P. Neuberg and M. Ripoll and F. Daubeuf and S. Erb and I. Dovgan and S. Ursuegui and S. Cianferani and A. Kichler and G. Chaubet and A. Wagner},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37376091},

doi = {10.3390/pharmaceutics15061643},

issn = {1999-4923 (Print) 

1999-4923 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Pharmaceutics},

volume = {15},

number = {6},

abstract = {Despite their clinical success, Antibody-Drug Conjugates (ADCs) are still limited to the delivery of a handful of cytotoxic small-molecule payloads. Adaptation of this successful format to the delivery of alternative types of cytotoxic payloads is of high interest in the search for novel anticancer treatments. Herein, we considered that the inherent toxicity of cationic nanoparticles (cNP), which limits their use as oligonucleotide delivery systems, could be turned into an opportunity to access a new family of toxic payloads. We complexed anti-HER2 antibody-oligonucleotide conjugates (AOC) with cytotoxic cationic polydiacetylenic micelles to obtain Antibody-Toxic-Nanoparticles Conjugates (ATNPs) and studied their physicochemical properties, as well as their bioactivity in both in vitro and in vivo HER2 models. After optimising their AOC/cNP ratio, the small (73 nm) HER2-targeting ATNPs were found to selectively kill antigen-positive SKBR-2 cells over antigen-negative MDA-MB-231 cells in serum-containing medium. Further in vivo anti-cancer activity was demonstrated in an SKBR-3 tumour xenograft model in BALB/c mice in which stable 60% tumour regression could be observed just after two injections of 45 pmol of ATNP. These results open interesting prospects in the use of such cationic nanoparticles as payloads for ADC-like strategies.},

note = {Lehot, Victor 

Neuberg, Patrick 

Ripoll, Manon 

Daubeuf, Francois 

Erb, Stephane 

Dovgan, Igor 

Ursuegui, Sylvain 

Cianferani, Sarah 

Kichler, Antoine 

Chaubet, Guilhem 

Wagner, Alain 

eng 

Switzerland 

2023/06/28 06:42 

Pharmaceutics. 2023 Jun 2;15(6):1643. doi: 10.3390/pharmaceutics15061643.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1882,

title = {Host cell protein quantification workflow using optimized standards combined with data-independent acquisition mass spectrometry},

author = {S. Hessmann and C. Chery and A. S. Sikora and A. Gervais and C. Carapito},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37305783},

doi = {10.1016/j.jpha.2023.03.009},

issn = {2214-0883 (Electronic) 

2214-0883 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {J Pharm Anal},

volume = {13},

number = {5},

pages = {494-502},

abstract = {Monitoring of host cell proteins (HCPs) during the manufacturing of monoclonal antibodies (mAb) has become a critical requirement to provide effective and safe drug products. Enzyme-linked immunosorbent assays are still the gold standard methods for the quantification of protein impurities. However, this technique has several limitations and does, among others, not enable the precise identification of proteins. In this context, mass spectrometry (MS) became an alternative and orthogonal method that delivers qualitative and quantitative information on all identified HCPs. However, in order to be routinely implemented in biopharmaceutical companies, liquid chromatography-MS based methods still need to be standardized to provide highest sensitivity and robust and accurate quantification. Here, we present a promising MS-based analytical workflow coupling the use of an innovative quantification standard, the HCP Profiler solution, with a spectral library-based data-independent acquisition (DIA) method and strict data validation criteria. The performances of the HCP Profiler solution were compared to more conventional standard protein spikes and the DIA approach was benchmarked against a classical data-dependent acquisition on a series of samples produced at various stages of the manufacturing process. While we also explored spectral library-free DIA interpretation, the spectral library-based approach still showed highest accuracy and reproducibility (coefficients of variation < 10%) with a sensitivity down to the sub-ng/mg mAb level. Thus, this workflow is today mature to be used as a robust and straightforward method to support mAb manufacturing process developments and drug products quality control.},

note = {Hessmann, Steve 

Chery, Cyrille 

Sikora, Anne-Sophie 

Gervais, Annick 

Carapito, Christine 

eng 

China 

2023/06/12 06:42 

J Pharm Anal. 2023 May;13(5):494-502. doi: 10.1016/j.jpha.2023.03.009. Epub 2023 Mar 31.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1892,

title = {Extended lifespan and improved genome stability in HepaRG-derived cell lines through reprogramming by high-density stress},

author = {C. Brun and C. Allain and P. J. Ferron and H. Younoussa and B. Colicchio and E. Jeandidier and R. M'Kacher and C. Guguen-Guillouzo and F. Bertile},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37639591},

doi = {10.1073/pnas.2219298120},

issn = {1091-6490 (Electronic) 

0027-8424 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Proc Natl Acad Sci U S A},

volume = {120},

number = {36},

pages = {e2219298120},

abstract = {The characteristics and fate of cancer cells partly depend on their environmental stiffness, i.e., the local mechanical cues they face. HepaRG progenitors are liver carcinoma cells exhibiting transdifferentiation properties; however, the underlying mechanisms remain unknown. To evaluate the impact of external physical forces mimicking the tumor microenvironment, we seeded them at very high density for 20 h, keeping the cells round and unanchored to the substrate. Applied without corticoids, spatial confinement due to very high density induced reprogramming of HepaRG cells into stable replicative stem-like cells after replating at normal density. Redifferentiation of these stem-like cells into cells very similar to the original HepaRG cells was then achieved using the same stress but in the presence of corticoids. This demonstrates that the cells retained the memory required to run the complete hepatic differentiation program, after bypassing the Hayflick limit twice. We show that physical stress improved chromosome quality and genomic stability, through greater efficiency of DNA repair and restoration of telomerase activity, thus enabling cells to escape progression to a more aggressive cancer state. We also show the primary importance of high-density seeding, possibly triggering compressive stress, in these processes, rather than that of cell roundness or intracellular tensional signals. The HepaRG-derived lines established here considerably extend the lifespan and availability of this surrogate cell system for mature human hepatocytes. External physical stress is a promising way to create a variety of cell lines, and it paves the way for the development of strategies to improve cancer prognosis.},

note = {Brun, Charlotte 

Allain, Coralie 

Ferron, Pierre-Jean 

Younoussa, Haifaou 

Colicchio, Bruno 

Jeandidier, Eric 

M'Kacher, Radhia 

Guguen-Guillouzo, Christiane 

Bertile, Fabrice 

eng 

Research Support, Non-U.S. Gov't 

2023/08/28 18:41 

Proc Natl Acad Sci U S A. 2023 Sep 5;120(36):e2219298120. doi: 10.1073/pnas.2219298120. Epub 2023 Aug 28.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1886,

title = {Mechanistic insights into sulfur source-driven physiological responses and metabolic reorganization in the fuel-biodesulfurizing 

 IGTS8},

author = {J. Zumsteg and A. Hirschler and C. Carapito and L. Maurer and C. Villette and D. Heintz and C. Dahl and A. El Nayal and V. Sangal and H. Mahmoud and A. Van Dorsselaer and W. Ismail},

url = {<Go to ISI>://WOS:001059796000001},

doi = {ARTN e0082623 

10.1128/aem.00826-23},

issn = {0099-2240},

year  = {2023},

date = {2023-01-01},

journal = {Applied and Environmental Microbiology},

abstract = {Comparative proteomics and untargeted metabolomics were combined to study the physiological and metabolic adaptations of Rhodococcus qingshengii IGTS8 under biodesulfurization conditions. After growth in a chemically defined medium with either dibenzothiophene (DBT) or MgSO4 as the sulfur source, many differentiallydifferentiallydifferentiallyproduced proteins and metabolites associated with several metabolic and physiological processes were detected including the metabolism of carbohydrates, amino acids, lipids, nucleotides, vitamins, protein synthesis, transcriptional regulation, cell envelope biogenesis, and cell division. Increased production of the redox cofactor mycofactocin and associated proteins was one of the most striking adaptations under biodesulfurization conditions. While most central metabolic enzymes were less abundant in the presence of DBT, a key enzyme of the glyoxylate shunt, isocitrate lyase, was up to 26-fold more abundant. Several C1 metabolism and oligotrophy-related enzymes were significantlysignificantly more abundant in the biodesulfurizing culture. R. qingshengii IGTS8 exhibited oligotrophic growth in liquid and solid media under carbon starvation. Moreover, the oligotrophic growth was faster on the solid medium in the presence of DBT compared to MgSO4 cultures. In the DBT culture, the cell envelope and phospholipids were remodeled, with lower levels of phosphatidylethanolamine and unsaturated and short-chain fatty acids being the most prominent changes. Biodesulfurization increased the biosynthesis of osmoprotectants (ectoine and mannosylglycerate) as well as glutamate and induced the stringent response. Our findings reveal highly diverse and overlapping stress responses that could protect the biodesulfurizing culture not only from the associated sulfate limitation but also from chemical, oxidative, and osmotic stress, allowing efficientefficient resource management. IMPORTANCE Despite decades of research, a commercially viable bioprocess for fuel desulfurization has not been developed yet. This is mainly due to lack of knowledge of the physiology and metabolism of fuel-biodesulfurizing bacteria. Being a stressful condition, biodesulfurization could provoke several stress responses that are not understood. This is particularly important because a thorough understanding of the microbial stress response is essential for the development of environmentally friendly and industrially efficientefficient microbial biocatalysts. Our comparative systems biology studies provide a mechanistic understanding of the biology of biodesulfurization, which is crucial for informed developments through the rational design of recombinant biodesulfurizers and optimization of the bioprocess conditions. Our findings enhance the understanding of the physiology, metabolism, and stress response not only in biodesulfurizing bacteria but also in rhodococci, a precious group of biotechnologically important bacteria.},

note = {Q8ei8 

Times Cited:0 

Cited References Count:125},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1876,

title = {N 2-methylguanosine modifications on human tRNAs and snRNA U6 are important for cell proliferation, protein translation and pre-mRNA splicing},

author = {C. Wang and N. Ulryck and L. Herzel and N. Pythoud and N. Kleiber and V. Guerineau and V. Jactel and C. Moritz and M. T. Bohnsack and C. Carapito and D. Touboul and K. E. Bohnsack and M. Graille},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37283053},

doi = {10.1093/nar/gkad487},

issn = {1362-4962 (Electronic) 

0305-1048 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Nucleic Acids Res},

abstract = {Modified nucleotides in non-coding RNAs, such as tRNAs and snRNAs, represent an important layer of gene expression regulation through their ability to fine-tune mRNA maturation and translation. Dysregulation of such modifications and the enzymes installing them have been linked to various human pathologies including neurodevelopmental disorders and cancers. Several methyltransferases (MTases) are regulated allosterically by human TRMT112 (Trm112 in Saccharomyces cerevisiae), but the interactome of this regulator and targets of its interacting MTases remain incompletely characterized. Here, we have investigated the interaction network of human TRMT112 in intact cells and identify three poorly characterized putative MTases (TRMT11, THUMPD3 and THUMPD2) as direct partners. We demonstrate that these three proteins are active N2-methylguanosine (m2G) MTases and that TRMT11 and THUMPD3 methylate positions 10 and 6 of tRNAs, respectively. For THUMPD2, we discovered that it directly associates with the U6 snRNA, a core component of the catalytic spliceosome, and is required for the formation of m2G, the last 'orphan' modification in U6 snRNA. Furthermore, our data reveal the combined importance of TRMT11 and THUMPD3 for optimal protein synthesis and cell proliferation as well as a role for THUMPD2 in fine-tuning pre-mRNA splicing.},

note = {Wang, Can 

Ulryck, Nathalie 

Herzel, Lydia 

Pythoud, Nicolas 

Kleiber, Nicole 

Guerineau, Vincent 

Jactel, Vincent 

Moritz, Chloe 

Bohnsack, Markus T 

Carapito, Christine 

Touboul, David 

Bohnsack, Katherine E 

Graille, Marc 

eng 

CSC/ 

469281184/Deutsche Forschungsgemeinschaft/ 

390729940/Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells/ 

ARC/ 

CNRS/ 

ANR-14-CE09-0016-02/Agence Nationale pour la Recherche/ 

Ecole Polytechnique/ 

AAP AIN INSB CNRS/ 

DIM MAP (Region Ile-de-France)/ 

ANR-20-CE29-0016/ANR Vapobio/ 

ANR-15-CE14-0013-02/Agence Nationale de la Recherche/ 

Region Grand-Est/ 

ProFI FR2048/French Proteomic Infrastructure/ 

England 

2023/06/07 06:42 

Nucleic Acids Res. 2023 Jun 7:gkad487. doi: 10.1093/nar/gkad487.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1906,

title = {Synthesis and Photochemical Properties of Fluorescent Metabolites Generated from Fluorinated Benzoylmenadiones in Living Cells},

author = {N. Trometer and B. Cichocki and Q. Chevalier and J. Pécourneau and J. M. Strub and A. Hemmerlin and A. Specht and E. Davioud-Charvet and M. Elhabiri},

url = {<Go to ISI>://WOS:001010309800001},

doi = {10.1021/acs.joc.3c00620},

issn = {0022-3263},

year  = {2023},

date = {2023-01-01},

journal = {Journal of Organic Chemistry},

volume = {89},

number = {4},

pages = {2104-2126},

abstract = {Thiswork describes the reactivity and properties of fluorinatedderivatives (F-PD and F-PDO) of plasmodione(PD) and its metabolite, the plasmodione oxide (PDO). Introduction of a fluorine atom on the 2-methyl groupmarkedly alters the redox properties of the 1,4-naphthoquinone electrophore,making the compound highly oxidizing and particularly photoreactive.A fruitful set of analytical methods (electrochemistry, absorptionand emission spectrophotometry, and HRMS-ESI) have been used to highlightthe products resulting from UV photoirradiation in the absence orpresence of selected nucleophiles. With F-PDO and inthe absence of nucleophile, photoreduction generates a highly reactive ortho-quinone methide (o-QM) capable ofleading to the formation of a homodimer. In the presence of thiolnucleophiles such as beta-mercaptoethanol, which was used as amodel, o-QMs are continuously regenerated in sequentialphotoredox reactions generating mono- or disulfanylation productsas well as various unreported sulfanyl products. Besides, these photoreducedadducts derived from F-PDO are characterized by a brightyellowish emission due to an excited-state intramolecular proton transfer(ESIPT) process between the dihydronapthoquinone and benzoyl units.In order to evidence the possibility of an intramolecular couplingof the o-QM intermediate, a synthetic route to thecorresponding anthrones is described. Tautomerization of the targetedanthrones occurs and affords highly fluorescent stable hydroxyl-anthraquinones.Although probable to explain the intense visible fluorescence emissionalso observed in tobacco BY-2 cells used as a cellular model, thesecoupling products have never been observed during the photochemicalreactions performed in this study. Our data suggest that the observedESIPT-induced fluorescence most likely corresponds to the generationof alkylated products through reduction species, as demonstrated withthe beta-mercaptoethanol model. In conclusion, F-PDO thus acts as a novel (pro)-fluorescent probe for monitoring redoxprocesses and protein alkylation in living cells.},

note = {Ia1z7 

Times Cited:1 

Cited References Count:77},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1899,

title = {Rapid Access to Potent Bispecific T Cell Engagers Using Biogenic Tyrosine Click Chemistry},

author = {I. Shajan and L. N. C. Rochet and S. R. Tracey and B. Jackowska and R. Benazza and O. Hernandez-Alba and S. Cianférani and C. J. Scott and F. L. Delft and V. Chudasama and B. Albada},

url = {<Go to ISI>://WOS:001129162800001},

doi = {10.1021/acs.bioconjchem.3c00357},

issn = {1043-1802},

year  = {2023},

date = {2023-01-01},

journal = {Bioconjugate Chemistry},

volume = {34},

number = {12},

pages = {2215-2220},

abstract = {Bispecific antibodies as T cell engagers designed to display binding capabilities to both tumor-associated antigens and antigens on T cells are considered promising agents in the fight against cancer. Even though chemical strategies to develop such constructs have emerged, a method that readily converts a therapeutically applied antibody into a bispecific construct by a fully non-genetic process is not yet available. Herein, we report the application of a biogenic, tyrosine-based click reaction utilizing chemoenzymatic modifications of native IgG1 antibodies to generate a synthetic bispecific antibody construct that exhibits tumor-killing capability at picomolar concentrations. Control experiments revealed that a covalent linkage of the different components is required for the observed biological activities. In view of the highly potent nature of the constructs and the modular approach that relies on convenient synthetic methods utilizing therapeutically approved biomolecules, our method expedites the production of potent bispecific antibody constructs with tunable cell killing efficacy with significant impact on therapeutic properties.},

note = {Cz9f5 

Times Cited:0 

Cited References Count:38},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1884,

title = {Membranes prime the RapGEF EPAC1 to transduce cAMP signaling},

author = {C. Sartre and F. Peurois and M. Ley and M. H. Kryszke and W. Zhang and D. Courilleau and R. Fischmeister and Y. Ambroise and M. Zeghouf and S. Cianferani and Y. Ferrandez and J. Cherfils},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37438343},

doi = {10.1038/s41467-023-39894-4},

issn = {2041-1723 (Electronic) 

2041-1723 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Nat Commun},

volume = {14},

number = {1},

pages = {4157},

abstract = {EPAC1, a cAMP-activated GEF for Rap GTPases, is a major transducer of cAMP signaling and a therapeutic target in cardiac diseases. The recent discovery that cAMP is compartmentalized in membrane-proximal nanodomains challenged the current model of EPAC1 activation in the cytosol. Here, we discover that anionic membranes are a major component of EPAC1 activation. We find that anionic membranes activate EPAC1 independently of cAMP, increase its affinity for cAMP by two orders of magnitude, and synergize with cAMP to yield maximal GEF activity. In the cell cytosol, where cAMP concentration is low, EPAC1 must thus be primed by membranes to bind cAMP. Examination of the cell-active chemical CE3F4 in this framework further reveals that it targets only fully activated EPAC1. Together, our findings reformulate previous concepts of cAMP signaling through EPAC proteins, with important implications for drug discovery.},

note = {Sartre, Candice 

Peurois, Francois 

Ley, Marie 

Kryszke, Marie-Helene 

Zhang, Wenhua 

Courilleau, Delphine 

Fischmeister, Rodolphe 

Ambroise, Yves 

Zeghouf, Mahel 

Cianferani, Sarah 

Ferrandez, Yann 

Cherfils, Jacqueline 

eng 

Research Support, Non-U.S. Gov't 

England 

2023/07/13 01:06 

Nat Commun. 2023 Jul 12;14(1):4157. doi: 10.1038/s41467-023-39894-4.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1904,

title = {Genetic Incorporation of Non-canonical Amino Acids in Anti-HER2 VHH: Expression and Characterization},

author = {N. Ramos and D. J. Bigot and G. Zeder-Lutz and J. M. Strub and A. Dagkesamanskaya and R. Fauré and S. Nouaille and C. Y. Montanier and G. Ferry and R. Wagner and S. Cianférani and J. A. Boutin and G. Truan},

doi = {10.37256/nat.5120243482},

year  = {2023},

date = {2023-01-01},

journal = {Nanoarchitectonics},

volume = {5 (1)},

pages = {24-42},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1880,

title = {Both age and social environment shape the phenotype of ant workers},

author = {M. Quque and C. Brun and C. Villette and C. Sueur and F. Criscuolo and D. Heintz and F. Bertile},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36604491},

doi = {10.1038/s41598-022-26515-1},

issn = {2045-2322 (Electronic) 

2045-2322 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Sci Rep},

volume = {13},

number = {1},

pages = {186},

abstract = {Position within the social group has consequences on individual lifespans in diverse taxa. This is especially obvious in eusocial insects, where workers differ in both the tasks they perform and their aging rates. However, in eusocial wasps, bees and ants, the performed task usually depends strongly on age. As such, untangling the effects of social role and age on worker physiology is a key step towards understanding the coevolution of sociality and aging. We performed an experimental protocol that allowed a separate analysis of these two factors using four groups of black garden ant (Lasius niger) workers: young foragers, old foragers, young nest workers, and old nest workers. We highlighted age-related differences in the proteome and metabolome of workers that were primarily related to worker subcaste and only secondarily to age. The relative abundance of proteins and metabolites suggests an improved xenobiotic detoxification, and a fuel metabolism based more on lipid use than carbohydrate use in young ants, regardless of their social role. Regardless of age, proteins related to the digestive function were more abundant in nest workers than in foragers. Old foragers were mostly characterized by weak abundances of molecules with an antibiotic activity or involved in chemical communication. Finally, our results suggest that even in tiny insects, extended lifespan may require to mitigate cancer risks. This is consistent with results found in eusocial rodents and thus opens up the discussion of shared mechanisms among distant taxa and the influence of sociality on life history traits such as longevity.},

note = {Quque, Martin 

Brun, Charlotte 

Villette, Claire 

Sueur, Cedric 

Criscuolo, Francois 

Heintz, Dimitri 

Bertile, Fabrice 

eng 

Research Support, Non-U.S. Gov't 

England 

2023/01/06 06:00 

Sci Rep. 2023 Jan 5;13(1):186. doi: 10.1038/s41598-022-26515-1.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1887,

title = {Honey Bee Larval Hemolymph as a Source of Key Nutrients and Proteins Offers a Promising Medium for 

 Artificial Rearing},

author = {V. Piou and C. Vilarem and S. Blanchard and J. M. Strub and F. Bertile and M. Bocquet and K. Arafah and P. Bulet and A. Vétillard},

url = {<Go to ISI>://WOS:001046249200001},

doi = {ARTN 12443 

10.3390/ijms241512443},

issn = {1661-6596},

year  = {2023},

date = {2023-01-01},

journal = {International Journal of Molecular Sciences},

volume = {24},

number = {15},

abstract = {Varroa destructor, a major ectoparasite of the Western honey bee Apis mellifera, is a widespread pest that damages colonies in the Northern Hemisphere. Throughout their lifecycle, V. destructor females feed on almost every developmental stage of their host, from the last larval instar to the adult. The parasite is thought to feed on hemolymph and fat body, although its exact diet and nutritional requirements are poorly known. Using artificial Parafilm & TRADE; dummies, we explored the nutrition of V. destructor females and assessed their survival when fed on hemolymph from bee larvae, pupae, or adults. We compared the results with mites fed on synthetic solutions or filtered larval hemolymph. The results showed that the parasites could survive for several days or weeks on different diets. Bee larval hemolymph yielded the highest survival rates, and filtered larval plasma was sufficient to maintain the mites for 14 days or more. This cell-free solution therefore theoretically contains all the necessary nutrients for mite survival. Because some bee proteins are known to be hijacked without being digested by the parasite, we decided to run a proteomic analysis of larval honey bee plasma to highlight the most common proteins in our samples. A list of 54 proteins was compiled, including several energy metabolism proteins such as Vitellogenin, Hexamerin, or Transferrins. These molecules represent key nutrient candidates that could be crucial for V. destructor survival.},

note = {O8ks6 

Times Cited:1 

Cited References Count:126},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1898,

title = {Reinvestigation of the Automated Synthesis of Stoichiometrically Conjugated Antibodies to Access High Molecular Weight Payloads and Multiplexed Conjugation via an In-Solution Trans-Tagging Process},

author = {V. Lehot and O. Lidicky and J. Most and S. Erb and I. Dovgan and A. Osypenko and O. Koniev and S. Kolodych and L. Kotrchova and G. Chaubet and S. Cianferani and T. Etrych and A. Wagner},

url = {<Go to ISI>://WOS:001089576600001},

doi = {10.1021/acsomega.3c05206},

issn = {2470-1343},

year  = {2023},

date = {2023-01-01},

journal = {Acs Omega},

volume = {8},

number = {43},

pages = {40508-40516},

abstract = {Protein conjugates have found applications in a widevariety offields, ranging from therapeutics to imaging and detection. However,robust control over the parameters of the conjugation process (suchas sites and degree of conjugation) remains challenging. Previously,our group introduced Equimolar NAtive Chemical Tagging (ENACT), amethod which allows for the monofunctionalization of proteins by combiningan iterative low-conversion bioconjugation, an automated process,and a bioorthogonal trans-tagging reaction. However, while the automatedENACT was dimensioned to achieve monoconjugation at the mg scale,in early stage research, because of the rarity and cost of the startingmaterials, it is often necessary to prepare conjugates at the lower,mu g, scale. Here, we introduce modified ENACT protocols, as wellas a new ENACT conjugation reagent, which allow for the monofunctionalizationof proteins on the micrograms scale, using minimal quantities of payload.},

note = {W3rz0 

Times Cited:0 

Cited References Count:13},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1901,

title = {Site-Selective Protein Conjugation by a Multicomponent Ugi Reaction},

author = {I. Koutsopetras and V. Vaur and R. Benazza and H. Diemer and C. Sornay and Y. Ersoy and L. Rochet and C. Longo and O. Hernandez-Alba and S. Erb and A. Detappe and A. Skerra and A. Wagner and S. Cianferani and G. Chaubet},

url = {https://www.ncbi.nlm.nih.gov/pubmed/38050774},

doi = {10.1002/chem.202303242},

issn = {1521-3765 (Electronic) 

0947-6539 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Chemistry},

pages = {e202303242},

abstract = {The chemical bioconjugation of proteins has seen tremendous applications in the past decades, with the booming of antibody-drug conjugates and their use in oncology. While genetic engineering has permitted to produce bespoke proteins featuring key (un-)natural amino acid residues poised for site-selective modifications, the conjugation of native proteins is riddled with selectivity issues. Chemoselective strategies are plentiful and enable the precise modification of virtually any residue with a reactive side-chain; site-selective methods are less common and usually most effective on small and medium-sized proteins. In this context, we studied the application of the Ugi multicomponent reaction for the site-selective conjugation of amine and carboxylate groups on proteins, and antibodies in particular. Through an in-depth mechanistic methodology work supported by peptide mapping studies, we managed to develop a set of conditions allowing the highly selective modification of antibodies bearing N-terminal glutamate and aspartate residues. We demonstrated that this strategy did not alter their affinity toward their target antigen and produced an antibody-drug conjugate with subnanomolar potency. Excitingly, we showed that the high site selectivity of our strategy was maintained on other protein formats, especially on anticalins, for which directed mutagenesis helped to highlight the key importance of a single lysine residue.},

note = {Koutsopetras, Ilias 

Vaur, Valentine 

Benazza, Rania 

Diemer, Helene 

Sornay, Charlotte 

Ersoy, Yagmur 

Rochet, Lea 

Longo, Carmen 

Hernandez-Alba, Oscar 

Erb, Stephane 

Detappe, Alexandre 

Skerra, Arne 

Wagner, Alain 

Cianferani, Sarah 

Chaubet, Guilhem 

eng 

Germany 

2023/12/05 12:42 

Chemistry. 2023 Dec 5:e202303242. doi: 10.1002/chem.202303242.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1891,

title = {Cysteine-Cysteine Cross-Conjugation of both Peptides and Proteins with a Bifunctional Hypervalent Iodine-Electrophilic Reagent},

author = {I. Koutsopetras and A. K. Mishra and R. Benazza and O. Hernandez-Alba and S. Cianferani and G. Chaubet and S. Nicolai and J. Waser},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37712523},

doi = {10.1002/chem.202302689},

issn = {1521-3765 (Electronic) 

0947-6539 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Chemistry},

pages = {e202302689},

abstract = {Peptide and protein bioconjugation sees ever-growing applications in the pharmaceutical sector. Novel strategies and reagents that can address the chemo- and regioselectivity issues inherent to these biomolecules, while delivering stable and functionalizable conjugates, are therefore needed. Herein, we introduce the crosslinking ethynylbenziodazolone (EBZ) reagent JW-AM-005 for the conjugation of peptides and proteins through the selective linkage of cysteine residues. This easily accessed compound gives access to peptide conjugates or stapled peptides under mild and tuneable conditions. Applied to the antibody fragment of antigen binding (Fab) species, JW-AM-005 delivered rebridged proteins in a one-pot three-reaction process with high regioselectivity, outperforming the standard reagents commonly used for this transformation.},

note = {Koutsopetras, Ilias 

Mishra, Abhaya Kumar 

Benazza, Rania 

Hernandez-Alba, Oscar 

Cianferani, Sarah 

Chaubet, Guilhem 

Nicolai, Stefano 

Waser, Jerome 

eng 

Germany 

2023/09/15 12:42 

Chemistry. 2023 Sep 15:e202302689. doi: 10.1002/chem.202302689.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1872,

title = {Bioactivated and PEG-Protected Circa 2 nm Gold Nanoparticles for in Cell Labelling and Cryo-Electron Microscopy},

author = {N. Groysbeck and V. Hanss and M. Donzeau and J. M. Strub and S. Cianferani and D. Spehner and M. Bahri and O. Ersen and M. Eltsov and P. Schultz and G. Zuber},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37035956},

doi = {10.1002/smtd.202300098},

issn = {2366-9608 (Electronic) 

2366-9608 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Small Methods},

volume = {7},

number = {6},

pages = {e2300098},

abstract = {Advances in cryo-electron microscopy (EM) enable imaging of protein assemblies within mammalian cells in a near native state when samples are preserved by cryogenic vitrification. To accompany this progress, specialized EM labelling protocols must be developed. Gold nanoparticles (AuNPs) of 2 nm are synthesized and functionalized to bind selected intracellular targets inside living human cells and to be detected in vitreous sections. As a proof of concept, thioaminobenzoate-, thionitrobenzoate-coordinated gold nanoparticles are functionalized on their surface with SV40 Nuclear Localization Signal (NLS)-containing peptides and 2 kDa polyethyleneglycols (PEG) by thiolate exchange to target the importin-mediated nuclear machinery and facilitate cytosolic diffusion by shielding the AuNP surface from non-specific binding to cell components, respectively. After delivery by electroporation into the cytoplasm of living human cells, the PEG-coated AuNPs diffuse freely in the cytoplasm but do not enter the nucleus. Incorporation of NLS within the PEG coverage promotes a quick nuclear import of the nanoparticles in relation to the density of NLS onto the AuNPs. Cryo-EM of vitreous cell sections demonstrate the presence of 2 nm AuNPs as single entities in the nucleus. Biofunctionalized AuNPs combined with live-cell electroporation procedures are thus potent labeling tools for the identification of macromolecules in cellular cryo-EM.},

note = {Groysbeck, Nadja 

Hanss, Victor 

Donzeau, Mariel 

Strub, Jean-Marc 

Cianferani, Sarah 

Spehner, Daniele 

Bahri, Mounib 

Ersen, Ovidiu 

Eltsov, Mikhael 

Schultz, Patrick 

Zuber, Guy 

eng 

ANR-10-IDEX-0002/ITI Innovec/ 

ANR-20-SFRI-0012/SFRI/ 

FRISBI ANR-10-INBS-05/French Infrastructure for Integrated Structural Biology/ 

22P096-00/ITMO Cancer/ 

Germany 

2023/04/11 06:00 

Small Methods. 2023 Jun;7(6):e2300098. doi: 10.1002/smtd.202300098. Epub 2023 Apr 10.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1897,

title = {Subcutaneous Administration of a Zwitterionic Chitosan-Based Hydrogel for Controlled Spatiotemporal Release of Monoclonal Antibodies},

author = {T. Grea and G. Jacquot and A. Durand and C. Mathieu and A. Gasser and C. Zhu and M. Banerjee and E. Hucteau and J. Mallard and P. L. Navarro and B. V. Popescu and E. Thomas and D. Kryza and J. Sidi-Boumedine and G. Ferrauto and E. Gianolio and G. Fleith and J. Combet and S. Brun and S. Erb and S. Cianferani and L. J. Charbonnière and L. Fellmann and C. Mirjolet and L. David and O. Tillement and F. Lux and S. Harlepp and X. Pivot and A. Detappe},

url = {<Go to ISI>://WOS:001129310000001},

doi = {10.1002/adma.202308738},

issn = {0935-9648},

year  = {2023},

date = {2023-01-01},

journal = {Advanced Materials},

abstract = {Subcutaneous (SC) administration of monoclonal antibodies (mAbs) is a proven strategy for improving therapeutic outcomes and patient compliance. The current FDA-/EMA-approved enzymatic approach, utilizing recombinant human hyaluronidase (rHuPH20) to enhance mAbs SC delivery, involves degrading the extracellular matrix's hyaluronate to increase tissue permeability. However, this method lacks tunable release properties, requiring individual optimization for each mAb. Seeking alternatives, physical polysaccharide hydrogels emerge as promising candidates due to their tunable physicochemical and biodegradability features. Unfortunately, none have demonstrated simultaneous biocompatibility, biodegradability, and controlled release properties for large proteins (>= 150 kDa) after SC delivery in clinical settings. Here, a novel two-component hydrogel comprising chitosan and chitosan@DOTAGA is introduced that can be seamlessly mixed with sterile mAbs formulations initially designed for intravenous (IV) administration, repurposing them as novel tunable SC formulations. Validated in mice and nonhuman primates (NHPs) with various mAbs, including trastuzumab and rituximab, the hydrogel exhibited biodegradability and biocompatibility features. Pharmacokinetic studies in both species demonstrated tunable controlled release, surpassing the capabilities of rHuPH20, with comparable parameters to the rHuPH20+mAbs formulation. These findings signify the potential for rapid translation to human applications, opening avenues for the clinical development of this novel SC biosimilar formulation. A novel hydrogel is developed using chitosan and chitosan@DOTAGA, enabling the repurposing of sterile monoclonal antibodies formulations designed for intravenous administration as tunable subcutaneous (SC) formulations. This hydrogel has demonstrated biodegradability, biocompatibility, and controlled release properties in mice and nonhuman primates, offering rapid translation to human use and potential for clinical development of SC biosimilars.image},

note = {Da4w7 

Times Cited:0 

Cited References Count:40},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1875,

title = {Benefits and Limitations of High-Resolution Cyclic IM-MS for Conformational Characterization of Native Therapeutic Monoclonal Antibodies},

author = {E. Desligniere and S. Ollivier and A. Beck and D. Ropartz and H. Rogniaux and S. Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36780376},

doi = {10.1021/acs.analchem.2c05265},

issn = {1520-6882 (Electronic) 

0003-2700 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Anal Chem},

volume = {95},

number = {8},

pages = {4162-4171},

abstract = {Monoclonal antibodies (mAbs) currently represent the main class of therapeutic proteins. mAbs approved by regulatory agencies are selected from IgG1, IgG2, and IgG4 subclasses, which possess different interchain disulfide connectivities. Ion mobility coupled to native mass spectrometry (IM-MS) has emerged as a valuable approach to tackle the challenging characterization of mAbs' higher order structures. However, due to the limited resolution of first-generation IM-MS instruments, subtle conformational differences on large proteins have long been hard to capture. Recent technological developments have aimed at increasing available IM resolving powers and acquisition mode capabilities, namely, through the release of high-resolution IM-MS (HR-IM-MS) instruments, like cyclic IM-MS (cIM-MS). Here, we outline the advantages and drawbacks of cIM-MS for better conformational characterization of intact mAbs ( approximately 150 kDa) in native conditions compared to first-generation instruments. We first assessed the extent to which multipass cIM-MS experiments could improve the separation of mAbs' conformers. These initial results evidenced some limitations of HR-IM-MS for large native biomolecules which possess rich conformational landscapes that remain challenging to decipher even with higher IM resolving powers. Conversely, for collision-induced unfolding (CIU) approaches, higher resolution proved to be particularly useful (i) to reveal new unfolding states and (ii) to enhance the separation of coexisting activated states, thus allowing one to apprehend gas-phase CIU behaviors of mAbs directly at the intact level. Altogether, this study offers a first panoramic overview of the capabilities of cIM-MS for therapeutic mAbs, paving the way for more widespread HR-IM-MS/CIU characterization of mAb-derived formats.},

note = {Desligniere, Evolene 

Ollivier, Simon 

Beck, Alain 

Ropartz, David 

Rogniaux, Helene 

Cianferani, Sarah 

eng 

Research Support, Non-U.S. Gov't 

2023/02/14 06:00 

Anal Chem. 2023 Feb 28;95(8):4162-4171. doi: 10.1021/acs.analchem.2c05265. Epub 2023 Feb 13.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1894,

title = {msqrob2PTM: differential abundance and differential usage analysis of MS-based proteomics data at the post-translational modification and peptidoform level},

author = {N. Demeulemeester and M. Gebelin and L. Caldi Gomes and P. Lingor and C. Carapito and L. Martens and L. Clement},

url = {https://www.ncbi.nlm.nih.gov/pubmed/38154689},

doi = {10.1016/j.mcpro.2023.100708},

issn = {1535-9484 (Electronic) 

1535-9476 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Mol Cell Proteomics},

pages = {100708},

abstract = {In the era of open-modification search engines, more post-translational modifications than ever can be detected by LC-MS/MS-based proteomics. This development can switch proteomics research into a higher gear, as PTMs are key in many cellular pathways important in cell proliferation, migration, metastasis and ageing. However, despite these advances in modification identification, statistical methods for PTM-level quantification and differential analysis have yet to catch up. This absence can partly be explained by statistical challenges inherent to the data, such as the confounding of PTM intensities with its parent protein abundance. Therefore, we have developed msqrob2PTM, a new workflow in the msqrob2 universe capable of differential abundance analysis at the PTM, and at the peptidoform level. The latter is important for validating PTMs found as significantly differential. Indeed, as our method can deal with multiple PTMs per peptidoform, there is a possibility that significant PTMs stem from one significant peptidoform carrying another PTM, hinting that it might be the other PTM driving the perceived differential abundance. Our workflows can flag both Differential Peptidoform (PTM) Abundance (DPA) and Differential Peptidoform (PTM) Usage (DPU). This enables a distinction between direct assessment of differential abundance of peptidoforms (DPA) and differences in the relative usage of peptidoforms corrected for corresponding protein abundances (DPU). For DPA, we directly model the log2-transformed peptidoform (PTM) intensities, while for DPU, we correct for parent protein abundance by an intermediate normalisation step which calculates the log2-ratio of the peptidoform (PTM) intensities to their summarized parent protein intensities. We demonstrated the utility and performance of msqrob2PTM by applying it to datasets with known ground truth, as well as to biological PTM-rich datasets. Our results show that msqrob2PTM is on par with, or surpassing the performance of, the current state-of-the-art methods. Moreover, msqrob2PTM is currently unique in providing output at the peptidoform level.},

note = {Demeulemeester, Nina 

Gebelin, Marie 

Caldi Gomes, Lucas 

Lingor, Paul 

Carapito, Christine 

Martens, Lennart 

Clement, Lieven 

eng 

2023/12/29 00:42 

Mol Cell Proteomics. 2023 Dec 26:100708. doi: 10.1016/j.mcpro.2023.100708.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1878,

title = {Updated MS(2)PIP web server supports cutting-edge proteomics applications},

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

url = {https://www.ncbi.nlm.nih.gov/pubmed/37140039},

doi = {10.1093/nar/gkad335},

issn = {1362-4962 (Electronic) 

0305-1048 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Nucleic Acids Res},

abstract = {Interest in the use of machine learning for peptide fragmentation spectrum prediction has been strongly on the rise over the past years, especially for applications in challenging proteomics identification workflows such as immunopeptidomics and the full-proteome identification of data independent acquisition spectra. Since its inception, the MS(2)PIP peptide spectrum predictor has been widely used for various downstream applications, mostly thanks to its accuracy, ease-of-use, and broad applicability. We here present a thoroughly updated version of the MS(2)PIP web server, which includes new and more performant prediction models for both tryptic- and non-tryptic peptides, for immunopeptides, and for CID-fragmented TMT-labeled peptides. Additionally, we have also added new functionality to greatly facilitate the generation of proteome-wide predicted spectral libraries, requiring only a FASTA protein file as input. These libraries also include retention time predictions from DeepLC. Moreover, we now provide pre-built and ready-to-download spectral libraries for various model organisms in multiple DIA-compatible spectral library formats. Besides upgrading the back-end models, the user experience on the MS(2)PIP web server is thus also greatly enhanced, extending its applicability to new domains, including immunopeptidomics and MS3-based TMT quantification experiments. MS(2)PIP is freely available at https://iomics.ugent.be/ms2pip/.},

note = {Declercq, Arthur 

Bouwmeester, Robbin 

Chiva, Cristina 

Sabido, Eduard 

Hirschler, Aurelie 

Carapito, Christine 

Martens, Lennart 

Degroeve, Sven 

Gabriels, Ralf 

eng 

12B7123N/Research Foundation Flanders/ 

HBC.2020.2205/Agentschap Innoveren en Ondernemen/ 

823839/European Union's Horizon 2020 Programme/ 

BOF21/GOA/033/Ghent University Concerted Research Action/ 

PID2020-115092GB-I00/Spanish Ministry of Science, Innovation and Universities/ 

England 

2023/05/04 12:41 

Nucleic Acids Res. 2023 May 4:gkad335. doi: 10.1093/nar/gkad335.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1881,

title = {Induction of ATF4-Regulated Atrogenes Is Uncoupled from Muscle Atrophy during Disuse in Halofuginone-Treated Mice and in Hibernating Brown Bears},

author = {L. Cussonneau and C. Coudy-Gandilhon and C. Deval and G. Chaouki and M. Djelloul-Mazouz and Y. Delorme and J. Hermet and G. Gauquelin-Koch and C. Polge and D. Taillandier and J. Averous and A. Bruhat and C. Jousse and I. Papet and F. Bertile and E. Lefai and P. Fafournoux and A. C. Maurin and L. Combaret},

url = {<Go to ISI>://WOS:000911048100001},

doi = {ARTN 621 

10.3390/ijms24010621},

year  = {2023},

date = {2023-01-01},

journal = {International Journal of Molecular Sciences},

volume = {24},

number = {1},

abstract = {Activating transcription factor 4 (ATF4) is involved in muscle atrophy through the overexpression of some atrogenes. However, it also controls the transcription of genes involved in muscle homeostasis maintenance. Here, we explored the effect of ATF4 activation by the pharmacological molecule halofuginone during hindlimb suspension (HS)-induced muscle atrophy. Firstly, we reported that periodic activation of ATF4-regulated atrogenes (Gadd45a, Cdkn1a, and Eif4ebp1) by halofuginone was not associated with muscle atrophy in healthy mice. Secondly, halofuginone-treated mice even showed reduced atrophy during HS, although the induction of the ATF4 pathway was identical to that in untreated HS mice. We further showed that halofuginone inhibited transforming growth factor-beta (TGF-beta) signalling, while promoting bone morphogenetic protein (BMP) signalling in healthy mice and slightly preserved protein synthesis during HS. Finally, ATF4-regulated atrogenes were also induced in the atrophy-resistant muscles of hibernating brown bears, in which we previously also reported concurrent TGF-beta inhibition and BMP activation. Overall, we show that ATF4-induced atrogenes can be uncoupled from muscle atrophy. In addition, our data also indicate that halofuginone can control the TGF-beta/BMP balance towards muscle mass maintenance. Whether halofuginone-induced BMP signalling can counteract the effect of ATF4-induced atrogenes needs to be further investigated and may open a new avenue to fight muscle atrophy. Finally, our study opens the way for further studies to identify well-tolerated chemical compounds in humans that are able to fine-tune the TGF-beta/BMP balance and could be used to preserve muscle mass during catabolic situations.},

note = {7s9cg 

Times Cited:1 

Cited References Count:74},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1900,

title = {Influence of pneumatic transportation on the stability of monoclonal antibodies},

author = {P. Coliat and S. Erb and H. Diemer and D. Karouby and T. Martin and M. Banerjee and C. Zhu and M. Demarchi and S. Cianferani and A. Detappe and X. Pivot},

url = {https://www.ncbi.nlm.nih.gov/pubmed/38072852},

doi = {10.1038/s41598-023-49235-6},

issn = {2045-2322 (Electronic) 

2045-2322 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Sci Rep},

volume = {13},

number = {1},

pages = {21875},

abstract = {Pneumatic transportation systems (PTS) were recently proposed as a method to carry ready-for-injection diluted monoclonal antibodies (mAbs) from the pharmacy to the bedside of patients. This method reduces transportation time and improves the efficiency of drug distribution process. However, mAbs are highly sensitive molecules for which subtle alterations may lead to deleterious clinical effects. These alterations can be caused by various external factors such as temperature, pH, pressure, and mechanical forces that may occur during transportation. Hence, it is essential to ensure that the mAbs transported by PTS remain stable and active throughout the transportation process. This study aims to determine the safety profile of PTS to transport 11 routinely used mAbs in a clinical setting through assessment of critical quality attributes (CQA) and orthogonal analysis. Hence, we performed aggregation/degradation profiling, post-translational modifications identification using complementary mass spectrometry-based methods, along with visible and subvisible particle formation determination by light absorbance and light obscuration analysis. Altogether, these results highlight that PTS can be safely used for this purpose when air is removed from the bags during preparation.},

note = {Coliat, Pierre 

Erb, Stephane 

Diemer, Helene 

Karouby, Dan 

Martin, Tristan 

Banerjee, Mainak 

Zhu, Chen 

Demarchi, Martin 

Cianferani, Sarah 

Detappe, Alexandre 

Pivot, Xavier 

eng 

England 

2023/12/11 00:42 

Sci Rep. 2023 Dec 10;13(1):21875. doi: 10.1038/s41598-023-49235-6.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1879,

title = {Towards a More Accurate Differential Analysis of Multiple Imputed Proteomics Data with mi4limma},

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

url = {https://www.ncbi.nlm.nih.gov/pubmed/36308688},

doi = {10.1007/978-1-0716-1967-4_7},

issn = {1940-6029 (Electronic) 

1064-3745 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Methods Mol Biol},

volume = {2426},

pages = {131-140},

abstract = {Imputing missing values is a common practice in label-free quantitative proteomics. Imputation replaces a missing value by a user-defined one. However, the imputation itself is not optimally considered downstream of the imputation process. In particular, imputed datasets are considered as if they had always been complete. The uncertainty due to the imputation is not properly taken into account. Hence, the mi4p package provides a more accurate statistical analysis of multiple-imputed datasets. A rigorous multiple imputation methodology is implemented, leading to a less biased estimation of parameters and their 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.},

note = {Chion, Marie 

Carapito, Christine 

Bertrand, Frederic 

eng 

Research Support, Non-U.S. Gov't 

2022/10/30 06:00 

Methods Mol Biol. 2023;2426:131-140. doi: 10.1007/978-1-0716-1967-4_7.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1890,

title = {Recent advances in structural mass spectrometry methods in the context of biosimilarity assessment: from sequence heterogeneities to higher order structures},

author = {J. Castel and S. Delaux and O. Hernandez-Alba and S. Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37713983},

doi = {10.1016/j.jpba.2023.115696},

issn = {1873-264X (Electronic) 

0731-7085 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {J Pharm Biomed Anal},

volume = {236},

pages = {115696},

abstract = {Biotherapeutics and their biosimilar versions have been flourishing in the biopharmaceutical market for several years. Structural and functional characterization is needed to achieve analytical biosimilarity through the assessment of critical quality attributes as required by regulatory authorities. The role of analytical strategies, particularly mass spectrometry-based methods, is pivotal to gathering valuable information for the in-depth characterization of biotherapeutics and biosimilarity assessment. Structural mass spectrometry methods (native MS, HDX-MS, top-down MS, etc.) provide information ranging from primary sequence assessment to higher order structure evaluation. This review focuses on recent developments and applications in structural mass spectrometry for biotherapeutic and biosimilar characterization.},

note = {Castel, Jerome 

Delaux, Sarah 

Hernandez-Alba, Oscar 

Cianferani, Sarah 

eng 

Review 

England 

2023/09/16 05:41 

J Pharm Biomed Anal. 2023 Nov 30;236:115696. doi: 10.1016/j.jpba.2023.115696. Epub 2023 Sep 9.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1873,

title = {Interlaboratory Evaluation of a User-Friendly Benchtop Mass Spectrometer for Multiple-Attribute Monitoring Studies of a Monoclonal Antibody},

author = {C. I. Butre and V. D'Atri and H. Diemer and O. Colas and E. Wagner and A. Beck and S. Cianferani and D. Guillarme and A. Delobel},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36985827},

doi = {10.3390/molecules28062855},

issn = {1420-3049 (Electronic) 

1420-3049 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Molecules},

volume = {28},

number = {6},

abstract = {In the quest to market increasingly safer and more potent biotherapeutic proteins, the concept of the multi-attribute method (MAM) has emerged from biopharmaceutical companies to boost the quality-by-design process development. MAM strategies rely on state-of-the-art analytical workflows based on liquid chromatography coupled to mass spectrometry (LC-MS) to identify and quantify a selected series of critical quality attributes (CQA) in a single assay. Here, we aimed at evaluating the repeatability and robustness of a benchtop LC-MS platform along with bioinformatics data treatment pipelines for peptide mapping-based MAM studies using standardized LC-MS methods, with the objective to benchmark MAM methods across laboratories, taking nivolumab as a case study. Our results evidence strong interlaboratory consistency across LC-MS platforms for all CQAs (i.e., deamidation, oxidation, lysine clipping and glycosylation). In addition, our work uniquely highlights the crucial role of bioinformatics postprocessing in MAM studies, especially for low-abundant species quantification. Altogether, we believe that MAM has fostered the development of routine, robust, easy-to-use LC-MS platforms for high-throughput determination of major CQAs in a regulated environment.},

note = {Butre, Claire I 

D'Atri, Valentina 

Diemer, Helene 

Colas, Olivier 

Wagner, Elsa 

Beck, Alain 

Cianferani, Sarah 

Guillarme, Davy 

Delobel, Arnaud 

eng 

ProFI; ANR-10-INBS-08-03/CNRS, the University of Strasbourg, the Agence Nationale de la Recherche, the French Proteomic Infrastructure/ 

Switzerland 

2023/03/30 06:00 

Molecules. 2023 Mar 22;28(6):2855. doi: 10.3390/molecules28062855.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1903,

title = {Diversifying the concept of model organisms in the age of -omics},

author = {F. Bertile and S. Matallana-Surget and A. Tholey and S. Cristobal and J. Armengaud},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37857885},

doi = {10.1038/s42003-023-05458-x},

issn = {2399-3642 (Electronic) 

2399-3642 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Commun Biol},

volume = {6},

number = {1},

pages = {1062},

abstract = {In today's post-genomic era, it is crucial to rethink the concept of model organisms. While a few historically well-established organisms, e.g. laboratory rodents, have enabled significant scientific breakthroughs, there is now a pressing need for broader inclusion. Indeed, new organisms and models, from complex microbial communities to holobionts, are essential to fully grasp the complexity of biological principles across the breadth of biodiversity. By fostering collaboration between biology, advanced molecular science and omics communities, we can collectively adopt new models, unraveling their molecular functioning, and uncovering fundamental mechanisms. This concerted effort will undoubtedly enhance human health, environmental quality, and biodiversity conservation.},

note = {Bertile, Fabrice 

Matallana-Surget, Sabine 

Tholey, Andreas 

Cristobal, Susana 

Armengaud, Jean 

eng 

Review 

England 

2023/10/20 00:43 

Commun Biol. 2023 Oct 19;6(1):1062. doi: 10.1038/s42003-023-05458-x.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1895,

title = {Improved characterization of trastuzumab deruxtecan with PTCR and internal fragments implemented in middle-down MS workflows},

author = {C. Beaumal and E. Deslignière and H. Diemer and C. Carapito and S. Cianfréani and O. Hernandez-Alba},

url = {<Go to ISI>://WOS:001117978100002},

doi = {10.1007/s00216-023-05059-x},

issn = {1618-2642},

year  = {2023},

date = {2023-01-01},

journal = {Analytical and Bioanalytical Chemistry},

abstract = {Antibody-drug conjugates (ADCs) are highly complex proteins mainly due to the structural microvariability of the mAb, along with the additional heterogeneity afforded by the bioconjugation process. Top-down (TD) and middle-down (MD) strategies allow the straightforward fragmentation of proteins to elucidate the conjugated amino acid residues. Nevertheless, these spectra are very crowded with multiple overlapping and unassigned ion fragments. Here we report on the use of dedicated software (ClipsMS) and application of proton transfer charge reduction (PTCR), to respectively expand the fragment ion search space to internal fragments and improve the separation of overlapping fragment ions for a more comprehensive characterization of a recently approved ADC, trastuzumab deruxtecan (T-DXd). Subunit fragmentation allowed between 70 and 90% of sequence coverage to be obtained. Upon addition of internal fragment assignment, the three subunits were fully sequenced, although internal fragments did not contribute significantly to the localization of the payloads. Finally, the use of PTCR after subunit fragmentation provided a moderate sequence coverage increase between 2 and 13%. The reaction efficiently decluttered the fragmentation spectra allowing increasing the number of fragment ions characteristic of the conjugation site by 1.5- to 2.5-fold. Altogether, these results show the interest in the implementation of internal fragment ion searches and more particularly the use of PTCR reactions to increase the number of signature ions to elucidate the conjugation sites and enhance the overall sequence coverage of ADCs, making this approach particularly appealing for its implementation in R&D laboratories.},

note = {Aj0j7 

Times Cited:0 

Cited References Count:49},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1877,

title = {Advanced mass spectrometry workflows for accurate quantification of trace-level host cell proteins in drug products: Benefits of FAIMS separation and gas-phase fractionation DIA},

author = {C. Beaumal and A. Beck and O. Hernandez-Alba and C. Carapito},

url = {https://www.ncbi.nlm.nih.gov/pubmed/37148167},

doi = {10.1002/pmic.202300172},

issn = {1615-9861 (Electronic) 

1615-9853 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Proteomics},

pages = {e2300172},

abstract = {Therapeutic monoclonal antibodies (mAb) production relies on multiple purification steps before release as a drug product (DP). A few host cell proteins (HCPs) may co-purify with the mAb. Their monitoring is crucial due to the considerable risk they represent for mAb stability, integrity, and efficacy and their potential immunogenicity. Enzyme-linked immunosorbent assays (ELISA) commonly used for global HCP monitoring present limitations in terms of identification and quantification of individual HCPs. Therefore, liquid chromatography tandem mass spectrometry (LC-MS/MS) has emerged as a promising alternative. Challenging DP samples show an extreme dynamic range requiring high performing methods to detect and reliably quantify trace-level HCPs. Here, we investigated the benefits of adding high-field asymmetric ion mobility spectrometry (FAIMS) separation and gas phase fractionation (GPF) prior to data independent acquisition (DIA). FAIMS LC-MS/MS analysis allowed the identification of 221 HCPs among which 158 were reliably quantified for a global amount of 880 ng/mg of NIST mAb Reference Material. Our methods have also been successfully applied to two FDA/EMA approved DPs and allowed digging deeper into the HCP landscape with the identification and quantification of a few tens of HCPs with sensitivity down to the sub-ng/mg of mAb level.},

note = {Beaumal, Corentin 

Beck, Alain 

Hernandez-Alba, Oscar 

Carapito, Christine 

eng 

ANR-10-INBS-08-03/Agence Nationale de la Recherche/ 

ProFI FR2048/Agence Nationale de la Recherche/ 

Ministere de l'Education Nationale, de l'Enseignement Superieur et de la Recherche/ 

Germany 

2023/05/06 19:41 

Proteomics. 2023 May 6:e2300172. doi: 10.1002/pmic.202300172.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1888,

title = {Toward countering muscle and bone loss with spaceflight: GSK3 as a potential target},

author = {R. W. Baranowski and J. L. Braun and B. L. Hockey and J. L. Yumol and M. S. Geromella and C. J. F. Watson and N. Kurgan and H. N. Messner and K. C. Whitley and A. J. MacNeil and G. Gauquelin-Koch and F. Bertile and W. Gittings and R. Vandenboom and W. E. Ward and V. A. Fajardo},

url = {<Go to ISI>://WOS:001056459200001},

doi = {ARTN 107047 

10.1016/j.isci.2023.107047},

year  = {2023},

date = {2023-01-01},

journal = {Iscience},

volume = {26},

number = {7},

abstract = {We examined the effects of similar to 30 days of spaceflight on glycogen synthase kinase 3 (GSK3) content and inhibitory serine phosphorylation in murine muscle and bone samples from four separate missions (BION-M1, rodent research [RR]1, RR9, and RR18). Spaceflight reduced GSK3 beta content across all missions, whereas its serine phosphorylation was elevated with RR18 and BION-M1. The reduction in GSK3 beta was linked to the reduction in type IIA fibers commonly observed with spaceflight as these fibers are particularly enriched with GSK3. We then tested the effects of inhibiting GSK3 before this fiber type shift, and we demonstrate that muscle-specific Gsk3 knockdown increased muscle mass, preserved muscle strength, and promoted the oxidative fiber type with Earth-based hindlimb unloading. In bone, GSK3 activation was enhanced after spaceflight; and strikingly, muscle-specific Gsk3 deletion increased bone mineral density in response to hindlimb unloading. Thus, future studies should test the effects of GSK3 inhibition during spaceflight.},

note = {Q3hn8 

Times Cited:0 

Cited References Count:50},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1905,

title = {Streptomyces cocklensis DSM 42063 and Actinacidiphila bryophytorum DSM 42138 colonize Arabidopsis thaliana and modulate its proteome},

author = {F. Arsène-Ploetze and M. Rompais and A. Alioua and V. Cognat and M. Erhardt and S. Graindorge and S. Koechler and J. Mutterer and C. Carapito and H. Schaller},

doi = {10.1094/PHYTOFR-12-22-0149-R},

year  = {2023},

date = {2023-01-01},

journal = {PhytoFrontiers},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1889,

title = {The interplay between lysosome, protein corona and biological effects of cationic carbon dots: Role of surface charge titratability},

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

url = {https://www.ncbi.nlm.nih.gov/pubmed/37683981},

doi = {10.1016/j.ijpharm.2023.123388},

issn = {1873-3476 (Electronic) 

0378-5173 (Linking)},

year  = {2023},

date = {2023-01-01},

journal = {Int J Pharm},

volume = {645},

pages = {123388},

abstract = {Carbon dots (CDs) are nanoparticles (NPs) with potential applications in the biomedical field. When in contact with biological fluids, most NPs are covered by a protein corona. As well, upon cell entry, most NP are sequestered in the lysosome. However, the interplay between the lysosome, the protein corona and the biological effects of NPs is still poorly understood. In this context, we investigated the role of the lysosome in the toxicological responses evoked by four cationic CDs exhibiting protonatable or non-protonatable amine groups at their surface, and the associated changes in the CD protein corona. The four CDs accumulated in the lysosome and led to lysosomal swelling, loss lysosome integrity, cathepsin B activation, NLRP3 inflammasome activation, and cell death by pyroptosis in a human macrophage model, but with a stronger effect for CDs with titratable amino groups. The protein corona formed around CDs in contact with serum partially dissociated under lysosomal conditions with subsequent protein rearrangement, as assessed by quantitative proteomic analysis. The residual protein corona still contained binding proteins, catalytic proteins, and proteins involved in the proteasome, glycolysis, or PI3k-Akt KEGG pathways, but with again a more pronounced effect for CDs with titratable amino groups. These results demonstrate an interplay between lysosome, protein corona and biological effects of cationic NPs in link with the titratability of NP surface charges.},

note = {Arezki, Yasmin 

Harmouch, Ezeddine 

Delalande, Francois 

Rapp, Mickael 

Schaeffer-Reiss, Christine 

Galli, Ophelie 

Cianferani, Sarah 

Lebeau, Luc 

Pons, Francoise 

Ronzani, Carole 

eng 

Netherlands 

2023/09/09 10:41 

Int J Pharm. 2023 Oct 15;645:123388. doi: 10.1016/j.ijpharm.2023.123388. Epub 2023 Sep 6.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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{RN1831,

title = {Repeated Exposure of Macrophages to Synthetic Amorphous Silica Induces Adaptive Proteome Changes and a Moderate Cell Activation},

author = {A. Torres and V. Collin-Faure and H. Diemer and C. Moriscot and D. Fenel and B. Gallet and S. Cianferani and J. A. Sergent and T. Rabilloud},

url = {<Go to ISI>://WOS:000795447400001},

doi = {ARTN 1424 

10.3390/nano12091424},

year  = {2022},

date = {2022-01-01},

journal = {Nanomaterials},

volume = {12},

number = {9},

abstract = {Synthetic amorphous silica (SAS) is a nanomaterial used in a wide variety of applications, including the use as a food additive. Two types of SAS are commonly employed as a powder additive, precipitated silica and fumed silica. Numerous studies have investigated the effects of synthetic amorphous silica on mammalian cells. However, most of them have used an exposure scheme based on a single dose of SAS. In this study, we have used instead a repeated 10-day exposure scheme in an effort to better simulate the occupational exposure encountered in daily life by consumers and workers. As a biological model, we have used the murine macrophage cell line J774A.1, as macrophages are very important innate immune cells in the response to particulate materials. In order to obtain a better appraisal of the macrophage responses to this repeated exposure to SAS, we have used proteomics as a wide-scale approach. Furthermore, some of the biological pathways detected as modulated by the exposure to SAS by the proteomic experiments have been validated through targeted experiments. Overall, proteomics showed that precipitated SAS induced a more important macrophage response than fumed SAS at equal dose. Nevertheless, validation experiments showed that most of the responses detected by proteomics are indeed adaptive, as the cellular homeostasis appeared to be maintained at the end of the exposure. For example, the intracellular glutathione levels or the mitochondrial transmembrane potential at the end of the 10 days exposure were similar for SAS-exposed cells and for unexposed cells. Similarly, no gross lysosomal damage was observed after repeated exposure to SAS. Nevertheless, important functions of macrophages such as phagocytosis, TNF alpha, and interleukin-6 secretion were up-modulated after exposure, as was the expression of important membrane proteins such as the scavenger receptors, MHC-II, or the MAC-1 receptor. These results suggest that repeated exposure to low doses of SAS slightly modulates the immune functions of macrophages, which may alter the homeostasis of the immune system.},

note = {2009/55},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1856,

title = {Large-Scale Conformational Changes of FhaC Provide Insights Into the Two-Partner Secretion Mechanism},

author = {G. Sicoli and A. Konijnenberg and J. Guerin and S. Hessmann and E. Del Nero and O. Hernandez-Alba and S. Lecher and G. Rouaut and L. Mueggenburg and H. Vezin and S. Cianferani and F. Sobott and R. Schneider and F. Jacob-Dubuisson},

url = {<Go to ISI>://WOS:000837116500001},

doi = {ARTN 950871 

10.3389/fmolb.2022.950871},

year  = {2022},

date = {2022-01-01},

journal = {Frontiers in Molecular Biosciences},

volume = {9},

abstract = {The Two-Partner secretion pathway mediates protein transport across the outer membrane of Gram-negative bacteria. TpsB transporters belong to the Omp85 superfamily, whose members catalyze protein insertion into, or translocation across membranes without external energy sources. They are composed of a transmembrane beta barrel preceded by two periplasmic POTRA domains that bind the incoming protein substrate. Here we used an integrative approach combining in vivo assays, mass spectrometry, nuclear magnetic resonance and electron paramagnetic resonance techniques suitable to detect minor states in heterogeneous populations, to explore transient conformers of the TpsB transporter FhaC. This revealed substantial, spontaneous conformational changes on a slow time scale, with parts of the POTRA2 domain approaching the lipid bilayer and the protein's surface loops. Specifically, our data indicate that an amphipathic POTRA2 beta hairpin can insert into the beta barrel. We propose that these motions enlarge the channel and initiate substrate secretion. Our data propose a solution to the conundrum how TpsB transporters mediate protein secretion without the need for cofactors, by utilizing intrinsic protein dynamics.},

note = {3o8wy 

Times Cited:0 

Cited References Count:77},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1840,

title = {Structural and Biochemical Investigation of the Heterodimeric Murine tRNA-Guanine Transglycosylase},

author = {M. Sebastiani and C. Behrens and S. Dorr and H. D. Gerber and R. Benazza and O. Hernandez-Alba and S. Cianferani and G. Klebe and A. Heine and K. Reuter},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35815944},

doi = {10.1021/acschembio.2c00368},

issn = {1554-8937 (Electronic) 

1554-8929 (Linking)},

year  = {2022},

date = {2022-01-01},

journal = {ACS Chem Biol},

abstract = {In tRNA(Asp), tRNA(Asn), tRNA(Tyr), and tRNA(His) of most bacteria and eukaryotes, the anticodon wobble position may be occupied by the modified nucleoside queuosine, which affects the speed and the accuracy of translation. Since eukaryotes are not able to synthesize queuosine de novo, they have to salvage queuine (the queuosine base) as a micronutrient from food and/or the gut microbiome. The heterodimeric Zn(2+) containing enzyme tRNA-guanine transglycosylase (TGT) catalyzes the insertion of queuine into the above-named tRNAs in exchange for the genetically encoded guanine. This enzyme has attracted medical interest since it was shown to be potentially useful for the treatment of multiple sclerosis. In addition, TGT inactivation via gene knockout leads to the suppressed cell proliferation and migration of certain breast cancer cells, which may render this enzyme a potential target for the design of compounds supporting breast cancer therapy. As a prerequisite to fully exploit the medical potential of eukaryotic TGT, we have determined and analyzed a number of crystal structures of the functional murine TGT with and without bound queuine. In addition, we have investigated the importance of two residues of its non-catalytic subunit on dimer stability and determined the Michaelis-Menten parameters of murine TGT with respect to tRNA and several natural and artificial nucleobase substrates. Ultimately, on the basis of available TGT crystal structures, we provide an entirely conclusive reaction mechanism for this enzyme, which in detail explains why the TGT-catalyzed insertion of some nucleobases into tRNA occurs reversibly while that of others is irreversible.},

note = {Sebastiani, Maurice 

Behrens, Christina 

Dorr, Stefanie 

Gerber, Hans-Dieter 

Benazza, Rania 

Hernandez-Alba, Oscar 

Cianferani, Sarah 

Klebe, Gerhard 

Heine, Andreas 

Reuter, Klaus 

eng 

2022/07/12 06:00 

ACS Chem Biol. 2022 Jul 11. doi: 10.1021/acschembio.2c00368.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1857,

title = {A Novel Family of Acid-Cleavable Linker Based on Cyclic Acetal Motifs for the Production of Antibody-Drug Conjugates with High Potency and Selectivity},

author = {T. Rady and L. Turelli and M. Nothisen and E. Tobaldi and S. Erb and F. Thoreau and O. Hernandez-Alba and S. Cianferani and F. Daubeuf and A. Wagner and G. Chaubet},

url = {https://www.ncbi.nlm.nih.gov/pubmed/36106863},

doi = {10.1021/acs.bioconjchem.2c00314},

issn = {1520-4812 (Electronic) 

1043-1802 (Linking)},

year  = {2022},

date = {2022-01-01},

journal = {Bioconjug Chem},

abstract = {Cleavable linkers have become the subject of intense study in the field of chemical biology, particularly because of their applications in the construction of antibody-drug conjugates (ADC), where they facilitate lysosomal cleavage and liberation of drugs from their carrier protein. Due to lysosomes' acidic nature, acid-labile motifs have attracted much attention, leading to the development of hydrazone and carbonate linkers among several other entities. Continuing our efforts in designing new moieties, we present here a family of cyclic acetals that exhibit excellent plasma stability and acid lability, notably in lysosomes. Incorporated in ADC, they led to potent constructs with picomolar potency in vitro and similar in vivo efficacy as the commercially available ADC Kadcyla in mouse xenograft models.},

note = {Rady, Tony 

Turelli, Lorenzo 

Nothisen, Marc 

Tobaldi, Elisabetta 

Erb, Stephane 

Thoreau, Fabien 

Hernandez-Alba, Oscar 

Cianferani, Sarah 

Daubeuf, Francois 

Wagner, Alain 

Chaubet, Guilhem 

eng 

2022/09/16 06:00 

Bioconjug Chem. 2022 Sep 15. doi: 10.1021/acs.bioconjchem.2c00314.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1829,

title = {Eusociality is linked to caste-specific differences in metabolism, immune system, and somatic maintenance-related processes in an ant species},

author = {M. Quque and C. Villette and F. Criscuolo and C. Sueur and F. Bertile and D. Heintz},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34971425},

doi = {10.1007/s00018-021-04024-0},

issn = {1420-9071 (Electronic) 

1420-682X (Linking)},

year  = {2022},

date = {2022-01-01},

journal = {Cell Mol Life Sci},

volume = {79},

number = {1},

pages = {29},

abstract = {The social organization of many primate, bird and rodent species and the role of individuals within that organization are associated with specific individual physiological traits. However, this association is perhaps most pronounced in eusocial insects (e.g., termites, ants). In such species, genetically close individuals show significant differences in behavior, physiology, and life expectancy. Studies addressing the metabolic changes according to the social role are still lacking. We aimed at understanding how sociality could influence essential molecular processes in a eusocial insect, the black garden ant (Lasius niger) where queens can live up to ten times longer than workers. Using mass spectrometry-based analysis, we explored the whole metabolome of queens, nest-workers and foraging workers. A former proteomics study done in the same species allowed us to compare the findings of both approaches. Confirming the former results at the proteome level, we showed that queens had fewer metabolites related to immunity. Contrary to our predictions, we did not find any metabolite linked to reproduction in queens. Among the workers, foragers had a metabolic signature reflecting a more stressful environment and a more highly stimulated immune system. We also found that nest-workers had more digestion-related metabolites. Hence, we showed that specific metabolic signatures match specific social roles. Besides, we identified metabolites differently expressed among behavioral castes and involved in nutrient sensing and longevity pathways (e.g., sirtuins, FOXO). The links between such molecular pathways and aging being found in an increasing number of taxa, our results confirm and strengthen their potential universality.},

note = {2015/29},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1839,

title = {A flexible and original architecture of two unrelated zinc fingers underlies the role of the multitask P1 in RYMV spread},

author = {V. Poignavent and F. Hoh and G. Terral and Y. Yang and F. X. Gillet and J. H. Kim and F. Allemand and E. Lacombe and C. Brugidou and S. Cianferani and H. Demene and F. Vignols},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35798161},

doi = {10.1016/j.jmb.2022.167715},

issn = {1089-8638 (Electronic) 

0022-2836 (Linking)},

year  = {2022},

date = {2022-01-01},

journal = {J Mol Biol},

pages = {167715},

abstract = {Viruses of the sobemovirus genus are plant viruses, most of which generate very important agricultural and financial losses. Among them, the rice yellow mottle virus (RYMV) is one of the most damaging pathogens devastating rice fields in Africa. RYMV infectivity and propagation rely on its protein P1, identified as a key movement and potential long-distance RNA silencing suppressor. Here we describe P1's complete 3D structure and dynamics obtained by an integrative approach combining X-Ray crystallography and NMR spectroscopy. We show that P1 is organized in two semi-independent and topologically unrelated domains, each harboring an original zinc finger. The two domains exhibit different affinities for zinc and sensitivities to oxidoreduction conditions, making the C-terminal P1 region a potential labile sensor of the plant redox status. An additional level of regulation resides on the capacity of P1 to oligomerize through its N-terminal domain. Coupling P1 structure information with site-directed mutagenesis and plant functional assays, we identified key residues in each zinc domain essential for infectivity and spread in rice tissues. Altogether, our results provide the first complete structure of a sobemoviral P1 movement protein and highlight structural and dynamical properties that may serve RYMV functions to infect and invade its host plant.},

note = {Poignavent, Vianney 

Hoh, Francois 

Terral, Guillaume 

Yang, Yinshan 

Gillet, Francois-Xavier 

Kim, Jeong-Hyeon 

Allemand, Frederic 

Lacombe, Eric 

Brugidou, Christophe 

Cianferani, Sarah 

Demene, Helene 

Vignols, Florence 

eng 

Netherlands 

2022/07/08 06:00 

J Mol Biol. 2022 Jul 4:167715. doi: 10.1016/j.jmb.2022.167715.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1836,

title = {Upconversion in a d-f [RuYb3] Supramolecular Assembly},

author = {R. C. Knighton and L. K. Soro and W. Thor and J. M. Strub and S. Cianferani and Y. Mely and M. Lenertz and K. L. Wong and C. Platas-Iglesias and F. Przybilla and L. J. Charbonniere},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35771602},

doi = {10.1021/jacs.2c05037},

issn = {1520-5126 (Electronic) 

0002-7863 (Linking)},

year  = {2022},

date = {2022-01-01},

journal = {J Am Chem Soc},

abstract = {We have prepared a hetero-tetrametallic assembly consisting of three ytterbium ions coordinated to a central [Ru(bpm)3](2+) (bpm = 2,2'-bipyrimidine) motif. Irradiation into the absorption band of the peripheral ytterbium ions at 980 nm engenders emission of the (3)MLCT state of the central [Ru(bpm)3](2+) core at 636 nm, which represents the first example of f –> d molecular upconversion (UC). Time-resolved measurements reveal a slow rise of the UC emission, which was modeled with a mathematical treatment of the observed kinetics according to a cooperative photosensitization mechanism using a virtual Yb centered doubly excited state followed by energy transfer to the Ru centered (1)MLCT state.},

note = {2021/02},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1835,

title = {Insights into the atypical autokinase activity of the Pseudomonas aeruginosa GacS histidine kinase and its interaction with RetS},

author = {F. Fadel and V. Bassim and V. I. Francis and S. L. Porter and T. Botzanowski and P. Legrand and M. M. Perez and Y. Bourne and S. Cianferani and F. Vincent},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35767996},

doi = {10.1016/j.str.2022.06.002},

issn = {1878-4186 (Electronic) 

0969-2126 (Linking)},

year  = {2022},

date = {2022-01-01},

journal = {Structure},

abstract = {Virulence in Pseudomonas aeruginosa (PA) depends on complex regulatory networks, involving phosphorelay systems based on two-component systems (TCSs). The GacS/GacA TCS is a master regulator of biofilm formation, swarming motility, and virulence. GacS is a membrane-associated unorthodox histidine kinase (HK) whose phosphorelay signaling pathway is inhibited by the RetS hybrid HK. Here we provide structural and functional insights into the interaction of GacS with RetS. The structure of the GacS-HAMP-H1 cytoplasmic regions reveals an unusually elongated homodimer marked by a 135 A long helical bundle formed by the HAMP, the signaling helix (S helix) and the DHp subdomain. The HAMP and S helix regions are essential for GacS signaling and contribute to the GacS/RetS binding interface. The structure of the GacS D1 domain together with the discovery of an unidentified functional ND domain, essential for GacS full autokinase activity, unveils signature motifs in GacS required for its atypical autokinase mechanism.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1859,

title = {Deciphering cellular and molecular determinants of human DPCD protein in complex with RUVBL1/RUVBL2 AAA-ATPases},

author = {R. Dos Santos Morais and P. E. Santo and M. Ley and C. Schelcher and Y. Abel and L. Plassart and E. Desligniere and M. E. Chagot and M. Quinternet and A. C. F. Paiva and S. Hessmann and N. Morellet and M. F. Sousa P and F. Vandermoere and E. Bertrand and B. Charpentier and T. M. Bandeiras and C. Plisson-Chastang and C. Verheggen and S. Cianferani and X. Manival},

url = {https://www.ncbi.nlm.nih.gov/pubmed/35901867},

doi = {10.1016/j.jmb.2022.167760},

issn = {1089-8638 (Electronic) 

0022-2836 (Linking)},

year  = {2022},

date = {2022-01-01},

journal = {J Mol Biol},

volume = {434},

number = {19},

pages = {167760},

abstract = {DPCD is a protein that may play a role in cilia formation and whose absence leads to primary ciliary dyskinesia (PCD), a rare disease caused by impairment of ciliated cells. Except for high-throughput studies that identified DPCD as a possible RUVBL1 (R1) and RUVBL2 (R2) partner, no in-depth cellular, biochemical, and structural investigation involving DPCD have been reported so far. R1 and R2 proteins are ubiquitous highly conserved AAA + family ATPases that assemble and mature a plethora of macromolecular complexes and are pivotal in numerous cellular processes, especially by guaranteeing a co-chaperoning function within R2TP or R2TP-like machineries. In the present study, we identified DPCD as a new R1R2 partner in vivo. We show that DPCD interacts directly with R1 and R2 in vitro and in cells. We characterized the physico-chemical properties of DPCD in solution and built a 3D model of DPCD. In addition, we used a variety of orthogonal biophysical techniques including small-angle X-ray scattering, structural mass spectrometry and electron microscopy to assess the molecular determinants of DPCD interaction with R1R2. Interestingly, DPCD disrupts the dodecameric state of R1R2 complex upon binding and this interaction occurs mainly via the DII domains of R1R2.},

note = {Dos Santos Morais, Raphael 

Santo, Paulo E 

Ley, Marie 

Schelcher, Cedric 

Abel, Yoann 

Plassart, Laura 

Desligniere, Evolene 

Chagot, Marie-Eve 

Quinternet, Marc 

Paiva, Ana C F 

Hessmann, Steve 

Morellet, Nelly 

M F Sousa, Pedro 

Vandermoere, Franck 

Bertrand, Edouard 

Charpentier, Bruno 

Bandeiras, Tiago M 

Plisson-Chastang, Celia 

Verheggen, Celine 

Cianferani, Sarah 

Manival, Xavier 

eng 

Netherlands 

2022/07/29 06:00 

J Mol Biol. 2022 Oct 15;434(19):167760. doi: 10.1016/j.jmb.2022.167760. Epub 2022 Jul 25.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}