@article{713,

title = {High-Resolution IMS-MS to Assign Additional Disulfide Bridge Pairing in Complementarity-Determining Regions of an IgG4 Monoclonal Antibody},

author = {E. Desligniere and T. Botzanowski and H. Diemer and D. A. Cooper-Shepherd and E. Wagner-Rousset and O. Colas and G. Bechade and K. Giles and O. Hernandez-Alba and A. Beck and S. Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34437803},

doi = {10.1021/jasms.1c00151},

issn = {1879-1123 (Electronic) 1044-0305 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {J Am Soc Mass Spectrom},

volume = {32},

number = {10},

pages = {2505-2512},

abstract = {Monoclonal antibodies (mAbs) have taken on an increasing importance for the treatment of various diseases, including cancers and immunological disorders. Disulfide bonds play a pivotal role in therapeutic antibody structure and activity relationships. Disulfide connectivity and cysteine-related variants are considered as critical quality attributes that must be monitored during mAb manufacturing and storage, as non-native disulfide bridges and aggregates might be responsible for loss of biological function and immunogenicity. The presence of cysteine residues in the complementarity-determining regions (CDRs) is rare in human antibodies but may be critical for the antigen-binding or deleterious for therapeutic antibody development. Consequently, in-depth characterization of their disulfide network is a prerequisite for mAb developability assessment. Mass spectrometry (MS) techniques represent powerful tools for accurate identification of disulfide connectivity. We report here on the MS-based characterization of an IgG4 comprising two additional cysteine residues in the CDR of its light chain. Classical bottom-up approaches after trypsin digestion first allowed identification of a dipeptide containing two disulfide bridges. To further investigate the conformational heterogeneity of the disulfide-bridged dipeptide, we performed ion mobility spectrometry-mass spectrometry (IMS-MS) experiments. Our results highlight benefits of high resolution IMS-MS to tackle the conformational landscape of disulfide peptides generated after trypsin digestion of a humanized IgG4 mAb under development. By comparing arrival time distributions of the mAb-collected and synthetic peptides, cyclic IMS afforded unambiguous assessment of disulfide bonds. In addition to classical peptide mapping, qualitative high-resolution IMS-MS can be of great interest to identify disulfide bonds within therapeutic mAbs.},

note = {Desligniere, Evolene 

Botzanowski, Thomas 

Diemer, Helene 

Cooper-Shepherd, Dale A 

Wagner-Rousset, Elsa 

Colas, Olivier 

Bechade, Guillaume 

Giles, Kevin 

Hernandez-Alba, Oscar 

Beck, Alain 

Cianferani, Sarah 

eng 

2021/08/27 06:00 

J Am Soc Mass Spectrom. 2021 Oct 6;32(10):2505-2512. doi: 10.1021/jasms.1c00151. Epub 2021 Aug 26.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{714,

title = {State-of-the-Art Native Mass Spectrometry and Ion Mobility Methods to Monitor Homogeneous Site-Specific Antibody-Drug Conjugates Synthesis},

author = {E. Desligniere and A. Ehkirch and B. L. Duivelshof and H. Toftevall and J. Sjogren and D. Guillarme and V. DÁtri and A. Beck and O. Hernandez-Alba and S. Cianferani},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34073805},

doi = {10.3390/ph14060498},

issn = {1424-8247 (Print) 1424-8247 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Pharmaceuticals (Basel)},

volume = {14},

number = {6},

abstract = {Antibody-drug conjugates (ADCs) are biotherapeutics consisting of a tumor-targeting monoclonal antibody (mAb) linked covalently to a cytotoxic drug. Early generation ADCs were predominantly obtained through non-selective conjugation methods based on lysine and cysteine residues, resulting in heterogeneous populations with varying drug-to-antibody ratios (DAR). Site-specific conjugation is one of the current challenges in ADC development, allowing for controlled conjugation and production of homogeneous ADCs. We report here the characterization of a site-specific DAR2 ADC generated with the GlyCLICK three-step process, which involves glycan-based enzymatic remodeling and click chemistry, using state-of-the-art native mass spectrometry (nMS) methods. The conjugation process was monitored with size exclusion chromatography coupled to nMS (SEC-nMS), which offered a straightforward identification and quantification of all reaction products, providing a direct snapshot of the ADC homogeneity. Benefits of SEC-nMS were further demonstrated for forced degradation studies, for which fragments generated upon thermal stress were clearly identified, with no deconjugation of the drug linker observed for the T-GlyGLICK-DM1 ADC. Lastly, innovative ion mobility-based collision-induced unfolding (CIU) approaches were used to assess the gas-phase behavior of compounds along the conjugation process, highlighting an increased resistance of the mAb against gas-phase unfolding upon drug conjugation. Altogether, these state-of-the-art nMS methods represent innovative approaches to investigate drug loading and distribution of last generation ADCs, their evolution during the bioconjugation process and their impact on gas-phase stabilities. We envision nMS and CIU methods to improve the conformational characterization of next generation-empowered mAb-derived products such as engineered nanobodies, bispecific ADCs or immunocytokines.},

note = {Desligniere, Evolene 

Ehkirch, Anthony 

Duivelshof, Bastiaan L 

Toftevall, Hanna 

Sjogren, Jonathan 

Guillarme, Davy 

DÁtri, Valentina 

Beck, Alain 

Hernandez-Alba, Oscar 

Cianferani, Sarah 

eng 

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

Switzerland 

2021/06/03 06:00 

Pharmaceuticals (Basel). 2021 May 24;14(6). pii: ph14060498. doi: 10.3390/ph14060498.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{723,

title = {Hibernating brown bears are protected against atherogenic dyslipidemia},

author = {S. Giroud and I. Chery and M. Arrive and M. Prost and J. Zumsteg and D. Heintz and A. L. Evans and G. Gauquelin-Koch and J. M. Arnemo and J. E. Swenson and E. Lefai and F. Bertile and C. Simon and S. Blanc},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34548543},

doi = {10.1038/s41598-021-98085-7},

issn = {2045-2322 (Electronic) 2045-2322 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Sci Rep},

volume = {11},

number = {1},

pages = {18723},

abstract = {To investigate mechanisms by which hibernators avoid atherogenic hyperlipidemia during hibernation, we assessed lipoprotein and cholesterol metabolisms of free-ranging Scandinavian brown bears (Ursus arctos). In winter- and summer-captured bears, we measured lipoprotein sizes and sub-classes, triglyceride-related plasma-enzyme activities, and muscle lipid composition along with plasma-levels of antioxidant capacities and inflammatory markers. Although hibernating bears increased nearly all lipid levels, a 36%-higher cholesteryl-ester transfer-protein activity allowed to stabilize lipid composition of high-density lipoproteins (HDL). Levels of inflammatory metabolites, i.e., 7-ketocholesterol and 11ss-prostaglandin F2alpha, declined in winter and correlated inversely with cardioprotective HDL2b-proportions and HDL-sizes that increased during hibernation. Lower muscle-cholesterol concentrations and lecithin-cholesterol acyltransferase activity in winter suggest that hibernating bears tightly controlled peripheral-cholesterol synthesis and/or release. Finally, greater plasma-antioxidant capacities prevented excessive lipid-specific oxidative damages in plasma and muscles of hibernating bears. Hence, the brown bear manages large lipid fluxes during hibernation, without developing adverse atherogenic effects that occur in humans and non-hibernators.},

note = {Giroud, Sylvain 

Chery, Isabelle 

Arrive, Mathilde 

Prost, Michel 

Zumsteg, Julie 

Heintz, Dimitri 

Evans, Alina L 

Gauquelin-Koch, Guillemette 

Arnemo, Jon M 

Swenson, Jon E 

Lefai, Etienne 

Bertile, Fabrice 

Simon, Chantal 

Blanc, Stephane 

eng 

P 31577-B25/Austrian Science Fund 

England 

2021/09/23 06:00 

Sci Rep. 2021 Sep 21;11(1):18723. doi: 10.1038/s41598-021-98085-7.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{724,

title = {Cardiomyocyte Protection by Hibernating Brown Bear Serum: Toward the Identification of New Protective Molecules Against Myocardial Infarction},

author = {L. Givre and C. Crola Da Silva and J. E. Swenson and J. M. Arnemo and G. Gauquelin-Koch and F. Bertile and E. Lefai and L. Gomez},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34336951},

doi = {10.3389/fcvm.2021.687501},

issn = {2297-055X (Print) 2297-055X (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Front Cardiovasc Med},

volume = {8},

pages = {687501},

abstract = {Ischemic heart disease remains one of the leading causes of death worldwide. Despite intensive research on the treatment of acute myocardial infarction, no effective therapy has shown clinical success. Therefore, novel therapeutic strategies are required to protect the heart from reperfusion injury. Interestingly, despite physical inactivity during hibernation, brown bears (Ursus arctos) cope with cardiovascular physiological conditions that would be detrimental to humans. We hypothesized that bear serum might contain circulating factors that could provide protection against cell injury. In this study, we sought to determine whether addition of bear serum might improve cardiomyocyte survival following hypoxia-reoxygenation. Isolated mouse cardiomyocytes underwent 45 min of hypoxia followed by reoxygenation. At the onset of reoxygenation, cells received fetal bovine serum (FBS; positive control), summer (SBS) or winter bear serum (WBS), or adult serums of other species, as indicated. After 2 h of reoxygenation, propidium iodide staining was used to evaluate cell viability by flow cytometry. Whereas, 0.5% SBS tended to decrease reperfusion injury, 0.5% WBS significantly reduced cell death, averaging 74.04 +/- 7.06% vs. 79.20 +/- 6.53% in the FBS group. This cardioprotective effect was lost at 0.1%, became toxic above 5%, and was specific to the bear. Our results showed that bear serum exerts a therapeutic effect with an efficacy threshold, an optimal dose, and a toxic effect on cardiomyocyte viability after hypoxia-reoxygenation. Therefore, the bear serum may be a potential source for identifying new therapeutic molecules to fight against myocardial reperfusion injury and cell death in general.},

note = {Givre, Lucas 

Crola Da Silva, Claire 

Swenson, Jon E 

Arnemo, Jon M 

Gauquelin-Koch, Guillemette 

Bertile, Fabrice 

Lefai, Etienne 

Gomez, Ludovic 

eng 

Switzerland 

2021/08/03 06:00 

Front Cardiovasc Med. 2021 Jul 16;8:687501. doi: 10.3389/fcvm.2021.687501. eCollection 2021.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{719,

title = {Biodesulfurization Induces Reprogramming of Sulfur Metabolism in Rhodococcus qingshengii IGTS8: Proteomics and Untargeted Metabolomics},

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

url = {https://www.ncbi.nlm.nih.gov/pubmed/34468196},

doi = {10.1128/Spectrum.00692-21},

issn = {2165-0497 (Electronic) 2165-0497 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Microbiol Spectr},

pages = {e0069221},

abstract = {Sulfur metabolism in fuel-biodesulfurizing bacteria and the underlying physiological adaptations are not understood, which has impeded the development of a commercially viable bioprocess for fuel desulfurization. To fill these knowledge gaps, we performed comparative proteomics and untargeted metabolomics in cultures of the biodesulfurization reference strain Rhodococcus qingshengii IGTS8 grown on either inorganic sulfate or the diesel-borne organosulfur compound dibenzothiophene as a sole sulfur source. Dibenzothiophene significantly altered the biosynthesis of many sulfur metabolism proteins and metabolites in a growth phase-dependent manner, which enabled us to reconstruct the first experimental model for sulfur metabolism in a fuel-biodesulfurizing bacterium. All key pathways related to assimilatory sulfur metabolism were represented in the sulfur proteome, including uptake of the sulfur sources, sulfur acquisition, and assimilatory sulfate reduction, in addition to biosynthesis of key sulfur-containing metabolites such as S-adenosylmethionine, coenzyme A, biotin, thiamin, molybdenum cofactor, mycothiol, and ergothioneine (low-molecular weight thiols). Fifty-two proteins exhibited significantly different abundance during at least one growth phase. Sixteen proteins were uniquely detected and 47 proteins were significantly more abundant in the dibenzothiophene culture during at least one growth phase. The sulfate-free dibenzothiophene-containing culture reacted to sulfate starvation by restricting sulfur assimilation, enforcing sulfur-sparing, and maintaining redox homeostasis. Biodesulfurization triggered alternative pathways for sulfur assimilation different from those operating in the inorganic sulfate culture. Sulfur metabolism reprogramming and metabolic switches in the dibenzothiophene culture were manifested in limiting sulfite reduction and biosynthesis of cysteine, while boosting the production of methionine via the cobalamin-independent pathway, as well as the biosynthesis of the redox buffers mycothiol and ergothioneine. The omics data underscore the key role of sulfur metabolism in shaping the biodesulfurization phenotype and highlight potential targets for improving the biodesulfurization catalytic activity via metabolic engineering. IMPORTANCE For many decades, research on biodesulfurization of fossil fuels was conducted amid a large gap in knowledge of sulfur metabolism and its regulation in fuel-biodesulfurizing bacteria, which has impeded the development of a commercially viable bioprocess. In addition, lack of understanding of biodesulfurization-associated metabolic and physiological adaptations prohibited the development of efficient biodesulfurizers. Our integrated omics-based findings reveal the assimilatory sulfur metabolism in the biodesulfurization reference strain Rhodococcus qingshengii IGTS8 and show how sulfur metabolism and oxidative stress response were remodeled and orchestrated to shape the biodesulfurization phenotype. Our findings not only explain the frequently encountered low catalytic activity of native fuel-biodesulfurizing bacteria but also uncover unprecedented potential targets in sulfur metabolism that could be exploited via metabolic engineering to boost the biodesulfurization catalytic activity, a prerequisite for commercial application.},

note = {Hirschler, Aurelie 

Carapito, Christine 

Maurer, Loic 

Zumsteg, Julie 

Villette, Claire 

Heintz, Dimitri 

Dahl, Christiane 

Al-Nayal, Ashraf 

Sangal, Vartul 

Mahmoud, Huda 

Van Dorsselaer, Alain 

Ismail, Wael 

eng 

2021/09/02 06:00 

Microbiol Spectr. 2021 Sep 1:e0069221. doi: 10.1128/Spectrum.00692-21.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{721,

title = {A spatial vascular transcriptomic, proteomic, and phosphoproteomic atlas unveils an angiocrine Tie-Wnt signaling axis in the liver},

author = {D. Inverso and J. Shi and K. H. Lee and M. Jakab and S. Ben-Moshe and S. R. Kulkarni and M. Schneider and G. Wang and M. Komeili and P. A. Velez and M. Riedel and C. Spegg and T. Ruppert and C. Schaeffer-Reiss and D. Helm and I. Singh and M. Boutros and S. Chintharlapalli and M. Heikenwalder and S. Itzkovitz and H. G. Augustin},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34038707},

doi = {10.1016/j.devcel.2021.05.001},

issn = {1878-1551 (Electronic) 1534-5807 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Dev Cell},

volume = {56},

number = {11},

pages = {1677-1693 e10},

abstract = {Single-cell transcriptomics (scRNA-seq) has revolutionized the understanding of the spatial architecture of tissue structure and function. Advancing the "transcript-centric" view of scRNA-seq analyses is presently restricted by the limited resolution of proteomics and genome-wide techniques to analyze post-translational modifications. Here, by combining spatial cell sorting with transcriptomics and quantitative proteomics/phosphoproteomics, we established the spatially resolved proteome landscape of the liver endothelium, yielding deep mechanistic insight into zonated vascular signaling mechanisms. Phosphorylation of receptor tyrosine kinases was detected preferentially in the central vein area, resulting in an atypical enrichment of tyrosine phosphorylation. Prototypic biological validation identified Tie receptor signaling as a selective and specific regulator of vascular Wnt activity orchestrating angiocrine signaling, thereby controlling hepatocyte function during liver regeneration. Taken together, the study has yielded fundamental insight into the spatial organization of liver endothelial cell signaling. Spatial sorting may be employed as a universally adaptable strategy for multiomic analyses of scRNA-seq-defined cellular (sub)-populations.},

note = {Inverso, Donato 

Shi, Jingjing 

Lee, Ki Hong 

Jakab, Moritz 

Ben-Moshe, Shani 

Kulkarni, Shubhada R 

Schneider, Martin 

Wang, Guanxiong 

Komeili, Marziyeh 

Velez, Paula Argos 

Riedel, Maria 

Spegg, Carleen 

Ruppert, Thomas 

Schaeffer-Reiss, Christine 

Helm, Dominic 

Singh, Indrabahadur 

Boutros, Michael 

Chintharlapalli, Sudhakar 

Heikenwalder, Mathias 

Itzkovitz, Shalev 

Augustin, Hellmut G 

eng 

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

2021/05/27 06:00 

Dev Cell. 2021 Jun 7;56(11):1677-1693.e10. doi: 10.1016/j.devcel.2021.05.001. Epub 2021 May 25.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{727,

title = {Vancomycin-decorated microbubbles as a theranostic agent for Staphylococcus aureus biofilms},

author = {J. J. P. Kouijzer and K. R. Lattwein and I. Beekers and S. A. G. Langeveld and M. Leon-Grooters and J. M. Strub and E. Oliva and G. L. A. Mislin and N. Jong and A. F. W. Steen and A. L. Klibanov and W. J. B. Wamel and K. Kooiman},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34624449},

doi = {10.1016/j.ijpharm.2021.121154},

issn = {1873-3476 (Electronic) 0378-5173 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Int J Pharm},

volume = {609},

pages = {121154},

abstract = {Bacterial biofilms are a huge burden on our healthcare systems worldwide. The lack of specificity in diagnostic and treatment possibilities result in difficult-to-treat and persistent infections. The aim of this in vitro study was to investigate if microbubbles targeted specifically to bacteria in biofilms could be used both for diagnosis as well for sonobactericide treatment and demonstrate their theranostic potential for biofilm infection management. The antibiotic vancomycin was chemically coupled to the lipid shell of microbubbles and validated using mass spectrometry and high-axial resolution 4Pi confocal microscopy. Theranostic proof-of-principle was investigated by demonstrating the specific binding of vancomycin-decorated microbubbles (vMB) to statically and flow grown Staphylococcus aureus (S. aureus) biofilms under increasing shear stress flow conditions (0-12 dyn/cm(2)), as well as confirmation of microbubble oscillation and biofilm disruption upon ultrasound exposure (2 MHz, 250 kPa, and 5,000 or 10,000 cycles) during flow shear stress of 5 dyn/cm(2) using time-lapse confocal microscopy combined with the Brandaris 128 ultra-high-speed camera. Vancomycin was successfully incorporated into the microbubble lipid shell. vMB bound significantly more often than control microbubbles to biofilms, also in the presence of free vancomycin (up to 1000 microg/mL) and remained bound under increasing shear stress flow conditions (up to 12 dyn/cm(2)). Upon ultrasound insonification biofilm area was reduced of up to 28%, as confirmed by confocal microscopy. Our results confirm the successful production of vMB and support their potential as a new theranostic tool for S. aureus biofilm infections by allowing for specific bacterial detection and biofilm disruption.},

note = {2021-02 (service chimie)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{725,

title = {Comparative Study of Secreted Proteins, Enzymatic Activities of Wood Degradation and Stilbene Metabolization in Grapevine Botryosphaeria Dieback Fungi},

author = {C. Labois and E. Stempien and J. Schneider and C. Schaeffer-Reiss and C. Bertsch and M. L. Goddard and J. Chong},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34356948},

doi = {10.3390/jof7070568},

issn = {2309-608X (Electronic) 2309-608X (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {J Fungi (Basel)},

volume = {7},

number = {7},

abstract = {Botryosphaeriaceae fungi are plant pathogens associated with Botryosphaeria dieback. To better understand the virulence factors of these fungi, we investigated the diversity of secreted proteins and extracellular enzyme activities involved in wood degradation and stilbene metabolization in Neofusicoccumparvum and Diplodiaseriata, which are two major fungi associated with grapevine B. dieback. Regarding the analysis of proteins secreted by the two fungi, our study revealed that N. parvum, known to be more aggressive than D. seriata, was characterized by a higher quantity and diversity of secreted proteins, especially hydrolases and oxidoreductases that are likely involved in cell wall and lignin degradation. In addition, when fungi were grown with wood powder, the extracellular laccase and Mn peroxidase enzyme activities were significantly higher in D. seriata compared to N.parvum. Importantly, our work also showed that secreted Botryosphaeriaceae proteins produced after grapevine wood addition are able to rapidly metabolize the grapevine stilbenes. Overall, a higher diversity of resveratrol and piceatannol metabolization products was found with enzymes of N. parvum compared to D. seriata. This study emphasizes the diversity of secreted virulence factors found in B. dieback fungi and suggests that some resveratrol oligomers produced in grapevine wood after pathogen attack could be formed via pathogenic fungal oxidases.},

note = {Labois, Clement 

Stempien, Elodie 

Schneider, Justine 

Schaeffer-Reiss, Christine 

Bertsch, Christophe 

Goddard, Mary-Lorene 

Chong, Julie 

eng 

72 2017 5191/Plan National Deperissement du Vignoble 

Switzerland 

2021/08/07 06:00 

J Fungi (Basel). 2021 Jul 16;7(7). pii: jof7070568. doi: 10.3390/jof7070568.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{715,

title = {Iron Stearate Structures: An Original Tool for Nanoparticles Design},

author = {F. Perton and G. Cotin and C. Kiefer and J. M. Strub and S. Cianferani and J. M. Greneche and N. Parizel and B. Heinrich and B. Pichon and D. Mertz and S. Begin-Colin},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34339179},

doi = {10.1021/acs.inorgchem.1c01689},

issn = {1520-510X (Electronic) 0020-1669 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Inorg Chem},

volume = {60},

number = {16},

pages = {12445-12456},

abstract = {Iron carboxylates are widely used as iron precursors in the thermal decomposition process or considered as in situ formed intermediate precursors. Their molecular and three-dimensional (3D)-structural nature has been shown to affect the shape, size, and composition of the resulting iron oxide nanoparticles (NPs). Among carboxylate precursors, stearates are particularly attractive because of their higher stability to aging and hydration and they are used as additives in many applications. Despite the huge interest of iron stearates, very few studies aimed up to now at deciphering their full metal-ligand structures and the mechanisms allowing us to achieve in a controlled manner the bottom-up NP formation. In this work, we have thus investigated the molecular structure and composition of two iron stearate precursors, synthesized by introducing either two (FeSt2) or three (FeSt3) stearate (St) chains. Interestingly, both iron stearates consist of lamellar structures with planes of iron polynuclear complexes (polycations) separated with stearate chains in all-trans conformation. The iron content in polycations was found very different between both iron stearates. Their detailed characterizations indicate that FeSt2 is mainly composed of [Fe3-(mu3-O)St6.xH2O]Cl, with no (or few) free stearate, whereas FeSt3 is a mixture of mainly [Fe7(mu3-O(H))6(mu2-OH)xSt12-2x]St with some [Fe3(mu3-O)St6.xH2O]St and free stearic acid. The formation of bigger polynuclear complexes with FeSt3 was related to higher hydrolysis and condensation rates within the iron(III) chloride solution compared to the iron(II) chloride solution. These data suggested a nucleation mechanism based on the condensation of polycation radicals generated by the catalytic departure of two stearate chains from an iron polycation-based molecule.},

note = {Perton, Francis 

Cotin, Geoffrey 

Kiefer, Celine 

Strub, Jean-Marc 

Cianferani, Sarah 

Greneche, Jean-Marc 

Parizel, Nathalie 

Heinrich, Benoit 

Pichon, Benoit 

Mertz, Damien 

Begin-Colin, Sylvie 

eng 

2021/08/03 06:00 

Inorg Chem. 2021 Aug 16;60(16):12445-12456. doi: 10.1021/acs.inorgchem.1c01689. Epub 2021 Aug 2.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{717,

title = {A proteomic-informed view of the changes induced by loss of cellular adherence: The example of mouse macrophages},

author = {S. Ramirez Rios and A. Torres and H. Diemer and V. Collin-Faure and S. Cianferani and L. Lafanechere and T. Rabilloud},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34048472},

doi = {10.1371/journal.pone.0252450},

issn = {1932-6203 (Electronic) 1932-6203 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {PLoS One},

volume = {16},

number = {5},

pages = {e0252450},

abstract = {Except cells circulating in the bloodstream, most cells in vertebrates are adherent. Studying the repercussions of adherence per se in cell physiology is thus very difficult to carry out, although it plays an important role in cancer biology, e.g. in the metastasis process. In order to study how adherence impacts major cell functions, we used a murine macrophage cell line. Opposite to the monocyte/macrophage system, where adherence is associated with the acquisition of differentiated functions, these cells can be grown in both adherent or suspension conditions without altering their differentiated functions (phagocytosis and inflammation signaling). We used a proteomic approach to cover a large panel of proteins potentially modified by the adherence status. Targeted experiments were carried out to validate the proteomic results, e.g. on metabolic enzymes, mitochondrial and cytoskeletal proteins. The mitochondrial activity was increased in non-adherent cells compared with adherent cells, without differences in glucose consumption. Concerning the cytoskeleton, a rearrangement of the actin organization (filopodia vs sub-cortical network) and of the microtubule network were observed between adherent and non-adherent cells. Taken together, these data show the mechanisms at play for the modification of the cytoskeleton and also modifications of the metabolic activity between adherent and non-adherent cells.},

note = {Ramirez Rios, Sacnite 

Torres, Anaelle 

Diemer, Helene 

Collin-Faure, Veronique 

Cianferani, Sarah 

Lafanechere, Laurence 

Rabilloud, Thierry 

eng 

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

2021/05/29 06:00 

PLoS One. 2021 May 28;16(5):e0252450. doi: 10.1371/journal.pone.0252450. eCollection 2021.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{718,

title = {Catestatin in innate immunity and Cateslytin-derived peptides against superbugs},

author = {F. Scavello and A. Mutschler and S. Helle and F. Schneider and S. Chasserot-Golaz and J. M. Strub and S. Cianferani and Y. Haikel and M. H. Metz-Boutigue},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34341386},

doi = {10.1038/s41598-021-94749-6},

issn = {2045-2322 (Electronic) 2045-2322 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Sci Rep},

volume = {11},

number = {1},

pages = {15615},

abstract = {Chromogranin A (CgA) is the precursor of several antimicrobial peptides, such as Catestatin (Cts, bovine CgA344-364), initially described as a potent inhibitor of catecholamines. This peptide displays direct antimicrobial activities and contributes to immune system regulation. The aim of the present study is to investigate a designed peptide based on Cts to fight infections against superbugs and more particularly Staphylococcus aureus. In addition to Cateslytin (Ctl, bovine CgA344-358), the active domain of Catestatin, several peptides including dimers, D-isomer and the new designed peptide DOPA-K-DOPA-K-DOPA-TLRGGE-RSMRLSFRARGYGFR (Dopa5T-Ctl) were prepared and tested. Cateslytin is resistant to bacterial degradation and does not induce bacterial resistance. The interaction of Catestatin with immune dermal cells (dendritic cells DC1a, dermal macrophages CD14 and macrophages) was analyzed by using confocal microscopy and cytokine release assay. The dimers and D-isomer of Ctl were tested against a large variety of bacteria showing the potent antibacterial activity of the D-isomer. The peptide Dopa5T-Ctl is able to induce the self-killing of S. aureus after release of Ctl by the endoprotease Glu-C produced by this pathogen. It permits localized on-demand delivery of the antimicrobial drug directly at the infectious site.},

note = {Scavello, Francesco 

Mutschler, Angela 

Helle, Sophie 

Schneider, Francis 

Chasserot-Golaz, Sylvette 

Strub, Jean-Marc 

Cianferani, Sarah 

Haikel, Youssef 

Metz-Boutigue, Marie-Helene 

eng 

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

England 

2021/08/04 06:00 

Sci Rep. 2021 Aug 2;11(1):15615. doi: 10.1038/s41598-021-94749-6.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1,

title = {A Proteomic- and Bioinformatic-Based Identification of Specific Allergens from Edible Insects: Probes for Future Detection as Food Ingredients},

author = {A. Barre and C. Pichereaux and M. Simplicien and O. Burlet-Schiltz and H. Benoist and P. Rouge},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33573235},

doi = {10.3390/foods10020280},

issn = {2304-8158 (Print) 2304-8158 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Foods},

volume = {10},

number = {2},

abstract = {The increasing development of edible insect flours as alternative sources of proteins added to food and feed products for improving their nutritional value, necessitates an accurate evaluation of their possible adverse side-effects, especially for individuals suffering from food allergies. Using a proteomic- and bioinformatic-based approach, the diversity of proteins occurring in currently consumed edible insects such as silkworm (Bombyx mori), cricket (Acheta domesticus), African migratory locust (Locusta migratoria), yellow mealworm (Tenebrio molitor), red palm weevil (Rhynchophorus ferrugineus), and giant milworm beetle (Zophobas atratus), was investigated. Most of them consist of phylogenetically-related protein allergens widely distributed in the different groups of arthropods (mites, insects, crustaceans) and mollusks. However, a few proteins belonging to discrete protein families including the chemosensory protein, hexamerin, and the odorant-binding protein, emerged as proteins highly specific for edible insects. To a lesser extent, other proteins such as apolipophorin III, the larval cuticle protein, and the receptor for activated protein kinase, also exhibited a rather good specificity for edible insects. These proteins, that are apparently missing or much less represented in other groups of arthropods, mollusks and nematods, share well conserved amino acid sequences and very similar three-dimensional structures. Owing to their ability to trigger allergic responses in sensitized people, they should be used as probes for the specific detection of insect proteins as food ingredients in various food products and thus, to assess their food safety, especially for people allergic to edible insects.},

note = {Barre, Annick 

Pichereaux, Carole 

Simplicien, Mathias 

Burlet-Schiltz, Odile 

Benoist, Herve 

Rouge, Pierre 

eng 

Switzerland 

2021/02/13 

Foods. 2021 Jan 30;10(2). pii: foods10020280. doi: 10.3390/foods10020280.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN22,

title = {The European Bioinformatics Community for Mass Spectrometry (EuBIC-MS): an open community for bioinformatics training and research},

author = {W. Bittremieux and D. Bouyssie and V. Dorfer and M. Locard-Paulet and Y. Perez-Riverol and V. Schwammle and J. Uszkoreit and T. Van Den Bossche},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33861485},

doi = {10.1002/rcm.9087},

issn = {1097-0231 (Electronic) 0951-4198 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Rapid Commun Mass Spectrom},

pages = {e9087},

abstract = {The European Bioinformatics Community for Mass Spectrometry (EuBIC-MS; eubic-ms.org) was founded in 2014 to unite European computational mass spectrometry researchers and proteomics bioinformaticians working in academia and industry. EuBIC-MS maintains educational resources (proteomics-academy.org) and organises workshops at national and international conferences on proteomics and mass spectrometry. Furthermore, EuBIC-MS is actively involved in several community initiatives such as the Human Proteome Organization's Proteomics Standards Initiative (HUPO-PSI). Apart from these collaborations, EuBIC-MS has organised two Winter Schools and two Developers' Meetings that have contributed to the strengthening of the European mass spectrometry network and fostered international collaboration in this field, even beyond Europe. Moreover, EuBIC-MS is currently actively developing a community-driven standard dedicated to mass spectrometry data annotation (SDRF-Proteomics) that will facilitate data reuse and collaboration. This manuscript highlights what EuBIC-MS is, what it does, and what it already has achieved. A warm invitation is extended to new researchers at all career stages to join the EuBIC-MS community on its Slack channel (eubic.slack.com).},

note = {Bittremieux, Wout 

Bouyssie, David 

Dorfer, Viktoria 

Locard-Paulet, Marie 

Perez-Riverol, Yasset 

Schwammle, Veit 

Uszkoreit, Julian 

Van Den Bossche, Tim 

eng 

12W0418N/Fonds Wetenschappelijk Onderzoek 

1S90918N/Fonds Wetenschappelijk Onderzoek 

NNF14CC0001/Novo Nordisk Fonden 

England 

2021/04/17 

Rapid Commun Mass Spectrom. 2021 Apr 16:e9087. doi: 10.1002/rcm.9087.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN2,

title = {RIOK2 phosphorylation by RSK promotes synthesis of the human small ribosomal subunit},

author = {E. L. Cerezo and T. Houles and O. Lie and M. K. Sarthou and C. Audoynaud and G. Lavoie and M. Halladjian and S. Cantaloube and C. Froment and O. Burlet-Schiltz and Y. Henry and P. P. Roux and A. K. Henras and Y. Romeo},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34125833},

doi = {10.1371/journal.pgen.1009583},

issn = {1553-7404 (Electronic) 1553-7390 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {PLoS Genet},

volume = {17},

number = {6},

pages = {e1009583},

abstract = {Ribosome biogenesis lies at the nexus of various signaling pathways coordinating protein synthesis with cell growth and proliferation. This process is regulated by well-described transcriptional mechanisms, but a growing body of evidence indicates that other levels of regulation exist. Here we show that the Ras/mitogen-activated protein kinase (MAPK) pathway stimulates post-transcriptional stages of human ribosome synthesis. We identify RIOK2, a pre-40S particle assembly factor, as a new target of the MAPK-activated kinase RSK. RIOK2 phosphorylation by RSK stimulates cytoplasmic maturation of late pre-40S particles, which is required for optimal protein synthesis and cell proliferation. RIOK2 phosphorylation facilitates its release from pre-40S particles and its nuclear re-import, prior to completion of small ribosomal subunits. Our results bring a detailed mechanistic link between the Ras/MAPK pathway and the maturation of human pre-40S particles, which opens a hitherto poorly explored area of ribosome biogenesis.},

note = {Cerezo, Emilie L 

Houles, Thibault 

Lie, Oriane 

Sarthou, Marie-Kerguelen 

Audoynaud, Charlotte 

Lavoie, Genevieve 

Halladjian, Maral 

Cantaloube, Sylvain 

Froment, Carine 

Burlet-Schiltz, Odile 

Henry, Yves 

Roux, Philippe P 

Henras, Anthony K 

Romeo, Yves 

eng 

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

2021/06/15 

PLoS Genet. 2021 Jun 14;17(6):e1009583. doi: 10.1371/journal.pgen.1009583. eCollection 2021 Jun.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN4c,

title = {Phosphoproteomics Identifies PI3K Inhibitor-selective Adaptive Responses in Pancreatic Cancer Cell Therapy and Resistance},

author = {C. Cintas and T. Douche and Z. Dantes and E. Mouton-Barbosa and M. P. Bousquet and C. Cayron and N. Therville and F. Pont and F. Ramos-Delgado and C. Guyon and B. Garmy-Susini and P. Cappello and O. Burlet-Schiltz and E. Hirsch and A. Gomez-Brouchet and B. Thibault and M. Reichert and J. Guillermet-Guibert},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34552006},

doi = {10.1158/1535-7163.MCT-20-0981},

issn = {1538-8514 (Electronic) 1535-7163 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Mol Cancer Ther},

volume = {20},

number = {12},

pages = {2433-2445},

abstract = {The PI3K pathway is highly active in human cancers. The four class I isoforms of PI3K are activated by distinct mechanisms leading to a common downstream signaling. Their downstream redundancy is thought to be responsible for treatment failures of PI3K inhibitors. We challenged this concept, by mapping the differential phosphoproteome evolution in response to PI3K inhibitors with different isoform-selectivity patterns in pancreatic cancer, a disease currently without effective therapy. In this cancer, the PI3K signal was shown to control cell proliferation. We compared the effects of LY294002 that inhibit with equal potency all class I isoenzymes and downstream mTOR with the action of inhibitors with higher isoform selectivity toward PI3Kalpha, PI3Kbeta, or PI3Kgamma (namely, A66, TGX-221 and AS-252424). A bioinformatics global pathway analysis of phosphoproteomics data allowed us to identify common and specific signals activated by PI3K inhibitors supported by the biological data. AS-252424 was the most effective treatment and induced apoptotic pathway activation as well as the highest changes in global phosphorylation-regulated cell signal. However, AS-252424 treatment induced reactivation of Akt, therefore decreasing the treatment outcome on cell survival. Reversely, AS-252424 and A66 combination treatment prevented p-Akt reactivation and led to synergistic action in cell lines and patient organoids. The combination of clinically approved alpha-selective BYL-719 with gamma-selective IPI-549 was more efficient than single-molecule treatment on xenograft growth. Mapping unique adaptive signaling responses to isoform-selective PI3K inhibition will help to design better combinative treatments that prevent the induction of selective compensatory signals.},

note = {Cintas, Celia 

Douche, Thibault 

Dantes, Zahra 

Mouton-Barbosa, Emmanuelle 

Bousquet, Marie-Pierre 

Cayron, Coralie 

Therville, Nicole 

Pont, Frederic 

Ramos-Delgado, Fernanda 

Guyon, Camille 

Garmy-Susini, Barbara 

Cappello, Paola 

Burlet-Schiltz, Odile 

Hirsch, Emilio 

Gomez-Brouchet, Anne 

Thibault, Benoit 

Reichert, Maximilian 

Guillermet-Guibert, Julie 

eng 

2021/09/24 

Mol Cancer Ther. 2021 Dec;20(12):2433-2445. doi: 10.1158/1535-7163.MCT-20-0981. Epub 2021 Sep 22.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN5d,

title = {Mass spectrometry-based proteomic analysis of parathyroid adenomas reveals PTH as a new human hormone-derived amyloid fibril protein},

author = {M. Colombat and B. Barres and C. Renaud and D. Ribes and S. Pericard and M. Camus and R. Anesia and N. Acker and D. Chauveau and O. Burlet-Schiltz and P. Brousset and S. Valleix},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33583309},

doi = {10.1080/13506129.2021.1885023},

issn = {1744-2818 (Electronic) 1350-6129 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Amyloid},

volume = {28},

number = {3},

pages = {153-157},

abstract = {BACKGROUND: Congo red-positive material was described in normal and diseased parathyroids (adenoma and hyperplasia) 50 years ago. However, the incidence and the clinical significance of such observation are unknown, and the causal fibril protein has never been convincingly demonstrated. METHODS: We conducted the present study including an exceptional case report accompanied with a retrospective study of 105 parathyroid adenomas. We used histopathological, immunohistochemical, ultrastructural, mass spectrometry-based proteomic analysis of parathyroid adenoma tissue samples, and genetic analysis. RESULTS: We describe a 57-year-old man with mild hypercalcemia and elevated parathyroid hormone (PTH) level for whom histopathological analysis revealed a parathyroid adenoma associated with nodular typical amyloid deposits. Tandem mass spectrometry after laser microdissection (LMD-MS) of amyloid adenoma identified PTH as the fibril protein, and no germline mutation in the PTH gene was detected. Congo red-positive PTH-deposits were further observed in 6.6% of the parathyroid adenomas analyzed, and were associated with complete/incomplete or absent universal amyloid signature, but with fibrillar morphology at ultrastructural level. CONCLUSIONS: Inappropriate PTH production leads to progressive disease-amyloid aggregation of PTH in a subset of parathyroid adenomas, providing new insights into the pathophysiology of this condition and adding PTH to the list of amyloid protein derived from hormones.},

note = {Colombat, Magali 

Barres, Beatrice 

Renaud, Claire 

Ribes, David 

Pericard, Sarah 

Camus, Mylene 

Anesia, Rodica 

van Acker, Nathalie 

Chauveau, Dominique 

Burlet-Schiltz, Odile 

Brousset, Pierre 

Valleix, Sophie 

eng 

England 

2021/02/16 

Amyloid. 2021 Sep;28(3):153-157. doi: 10.1080/13506129.2021.1885023. Epub 2021 Feb 13.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN21,

title = {A proteomics sample metadata representation for multiomics integration and big data analysis},

author = {C. Dai and A. Fullgrabe and J. Pfeuffer and E. M. Solovyeva and J. Deng and P. Moreno and S. Kamatchinathan and D. J. Kundu and N. George and S. Fexova and B. Gruning and M. C. Foll and J. Griss and M. Vaudel and E. Audain and M. Locard-Paulet and M. Turewicz and M. Eisenacher and J. Uszkoreit and T. Van Den Bossche and V. Schwammle and H. Webel and S. Schulze and D. Bouyssie and S. Jayaram and V. K. Duggineni and P. Samaras and M. Wilhelm and M. Choi and M. Wang and O. Kohlbacher and A. Brazma and I. Papatheodorou and N. Bandeira and E. W. Deutsch and J. A. Vizcaino and M. Bai and T. Sachsenberg and L. I. Levitsky and Y. Perez-Riverol},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34615866},

doi = {10.1038/s41467-021-26111-3},

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

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Nat Commun},

volume = {12},

number = {1},

pages = {5854},

abstract = {The amount of public proteomics data is rapidly increasing but there is no standardized format to describe the sample metadata and their relationship with the dataset files in a way that fully supports their understanding or reanalysis. Here we propose to develop the transcriptomics data format MAGE-TAB into a standard representation for proteomics sample metadata. We implement MAGE-TAB-Proteomics in a crowdsourcing project to manually curate over 200 public datasets. We also describe tools and libraries to validate and submit sample metadata-related information to the PRIDE repository. We expect that these developments will improve the reproducibility and facilitate the reanalysis and integration of public proteomics datasets.},

note = {Dai, Chengxin 

Fullgrabe, Anja 

Pfeuffer, Julianus 

Solovyeva, Elizaveta M 

Deng, Jingwen 

Moreno, Pablo 

Kamatchinathan, Selvakumar 

Kundu, Deepti Jaiswal 

George, Nancy 

Fexova, Silvie 

Gruning, Bjorn 

Foll, Melanie Christine 

Griss, Johannes 

Vaudel, Marc 

Audain, Enrique 

Locard-Paulet, Marie 

Turewicz, Michael 

Eisenacher, Martin 

Uszkoreit, Julian 

Van Den Bossche, Tim 

Schwammle, Veit 

Webel, Henry 

Schulze, Stefan 

Bouyssie, David 

Jayaram, Savita 

Duggineni, Vinay Kumar 

Samaras, Patroklos 

Wilhelm, Mathias 

Choi, Meena 

Wang, Mingxun 

Kohlbacher, Oliver 

Brazma, Alvis 

Papatheodorou, Irene 

Bandeira, Nuno 

Deutsch, Eric W 

Vizcaino, Juan Antonio 

Bai, Mingze 

Sachsenberg, Timo 

Levitsky, Lev I 

Perez-Riverol, Yasset 

eng 

208391/Z/17/Z/WT_/Wellcome Trust/United Kingdom 

R01 GM087221/GM/NIGMS NIH HHS/ 

Research Support, N.I.H., Extramural 

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

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

Review 

England 

2021/10/08 

Nat Commun. 2021 Oct 6;12(1):5854. doi: 10.1038/s41467-021-26111-3.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN18,

title = {Isoginkgetin derivative IP2 enhances the adaptive immune response against tumor antigens},

author = {R. Darrigrand and A. Pierson and M. Rouillon and D. Renko and M. Boulpicante and D. Bouyssie and E. Mouton-Barbosa and J. Marcoux and C. Garcia and M. Ghosh and M. Alami and S. Apcher},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33649389},

doi = {10.1038/s42003-021-01801-2},

issn = {2399-3642 (Electronic) 2399-3642 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Commun Biol},

volume = {4},

number = {1},

pages = {269},

abstract = {The success of cancer immunotherapy relies on the induction of an immunoprotective response targeting tumor antigens (TAs) presented on MHC-I molecules. We demonstrated that the splicing inhibitor isoginkgetin and its water-soluble and non-toxic derivative IP2 act at the production stage of the pioneer translation products (PTPs). We showed that IP2 increases PTP-derived antigen presentation in cancer cells in vitro and impairs tumor growth in vivo. IP2 action is long-lasting and dependent on the CD8(+) T cell response against TAs. We observed that the antigen repertoire displayed on MHC-I molecules at the surface of MCA205 fibrosarcoma is modified upon treatment with IP2. In particular, IP2 enhances the presentation of an exon-derived epitope from the tumor suppressor nischarin. The combination of IP2 with a peptide vaccine targeting the nischarin-derived epitope showed a synergistic antitumor effect in vivo. These findings identify the spliceosome as a druggable target for the development of epitope-based immunotherapies.},

note = {Darrigrand, Romain 

Pierson, Alison 

Rouillon, Marine 

Renko, Dolor 

Boulpicante, Mathilde 

Bouyssie, David 

Mouton-Barbosa, Emmanuelle 

Marcoux, Julien 

Garcia, Camille 

Ghosh, Michael 

Alami, Mouad 

Apcher, Sebastien 

eng 

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

England 

2021/03/03 

Commun Biol. 2021 Mar 1;4(1):269. doi: 10.1038/s42003-021-01801-2.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN7i,

title = {Mapping of the amniotic fluid proteome of fetuses with congenital anomalies of the kidney and urinary tract identifies plastin 3 as a protein involved in glomerular integrity},

author = {C. Fedou and M. Camus and O. Lescat and G. Feuillet and I. Mueller and B. Ross and M. Buleon and E. Neau and M. Alves and D. Goudouneche and B. Breuil and F. Boizard and Q. Bardou and A. Casemayou and I. Tack and S. Dreux and J. Batut and P. Blader and O. Burlet-Schiltz and S. Decramer and B. Wirth and J. Klein and J. S. Saulnier-Blache and B. Buffin-Meyer and J. P. Schanstra},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33987838},

doi = {10.1002/path.5703},

issn = {1096-9896 (Electronic) 0022-3417 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {J Pathol},

volume = {254},

number = {5},

pages = {575-588},

abstract = {Congenital anomalies of the kidney and the urinary tract (CAKUT) are the first cause of chronic kidney disease in childhood. Several genetic and environmental origins are associated with CAKUT, but most pathogenic pathways remain elusive. Considering the amniotic fluid (AF) composition as a proxy for fetal kidney development, we analyzed the AF proteome from non-severe CAKUT (n = 19), severe CAKUT (n = 14), and healthy control (n = 22) fetuses using LC-MS/MS. We identified 471 significant proteins that discriminated the three AF groups with 81% precision. Among them, eight proteins independent of gestational age (CSPG4, LMAN2, ENDOD1, ANGPTL2, PRSS8, NGFR, ROBO4, PLS3) were associated with both the presence and the severity of CAKUT. Among those, five were part of a protein-protein interaction network involving proteins previously identified as being potentially associated with CAKUT. The actin-bundling protein PLS3 (plastin 3) was the only protein displaying a gradually increased AF abundance from control, via non-severe, to severe CAKUT. Immunohistochemistry experiments showed that PLS3 was expressed in the human fetal as well as in both the fetal and the postnatal mouse kidney. In zebrafish embryos, depletion of PLS3 led to a general disruption of embryonic growth including reduced pronephros development. In postnatal Pls3-knockout mice, kidneys were macroscopically normal, but the glomerular ultrastructure showed thickening of the basement membrane and fusion of podocyte foot processes. These structural changes were associated with albuminuria and decreased expression of podocyte markers including Wilms' tumor-1 protein, nephrin, and podocalyxin. In conclusion, we provide the first map of the CAKUT AF proteome that will serve as a reference for future studies. Among the proteins strongly associated with CAKUT, PLS3 did surprisingly not specifically affect nephrogenesis but was found as a new contributor in the maintenance of normal kidney function, at least in part through the control of glomerular integrity. (c) 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.},

note = {Fedou, Camille 

Camus, Mylene 

Lescat, Ophelie 

Feuillet, Guylene 

Mueller, Ilka 

Ross, Bryony 

Buleon, Marie 

Neau, Eric 

Alves, Melinda 

Goudouneche, Dominique 

Breuil, Benjamin 

Boizard, Franck 

Bardou, Quentin 

Casemayou, Audrey 

Tack, Ivan 

Dreux, Sophie 

Batut, Julie 

Blader, Patrick 

Burlet-Schiltz, Odile 

Decramer, Stephane 

Wirth, Brunhilde 

Klein, Julie 

Saulnier-Blache, Jean Sebastien 

Buffin-Meyer, Benedicte 

Schanstra, Joost P 

eng 

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

England 

2021/05/15 

J Pathol. 2021 Aug;254(5):575-588. doi: 10.1002/path.5703. Epub 2021 Jun 16.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN8d,

title = {HA-MOP knockin mice express the canonical micro-opioid receptor but lack detectable splice variants},

author = {S. Fritzwanker and L. Mouledous and C. Mollereau and C. Froment and O. Burlet-Schiltz and F. Effah and A. Bailey and M. Spetea and R. K. Reinscheid and S. Schulz and A. Kliewer},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34522000},

doi = {10.1038/s42003-021-02580-6},

issn = {2399-3642 (Electronic) 2399-3642 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Commun Biol},

volume = {4},

number = {1},

pages = {1070},

abstract = {G protein-coupled receptors (GPCRs) are notoriously difficult to detect in native tissues. In an effort to resolve this problem, we have developed a novel mouse model by fusing the hemagglutinin (HA)-epitope tag sequence to the amino-terminus of the micro-opioid receptor (MOP). Although HA-MOP knock-in mice exhibit reduced receptor expression, we found that this approach allowed for highly efficient immunodetection of low abundant GPCR targets. We also show that the HA-tag facilitates both high-resolution imaging and immunoisolation of MOP. Mass spectrometry (MS) confirmed post-translational modifications, most notably agonist-selective phosphorylation of carboxyl-terminal serine and threonine residues. MS also unequivocally identified the carboxyl-terminal (387)LENLEAETAPLP(398) motif, which is part of the canonical MOP sequence. Unexpectedly, MS analysis of brain lysates failed to detect any of the 15 MOP isoforms that have been proposed to arise from alternative splicing of the MOP carboxyl-terminus. For quantitative analysis, we performed multiple successive rounds of immunodepletion using the well-characterized rabbit monoclonal antibody UMB-3 that selectively detects the (387)LENLEAETAPLP(398) motif. We found that >98% of HA-tagged MOP contain the UMB-3 epitope indicating that virtually all MOP expressed in the mouse brain exhibit the canonical amino acid sequence.},

note = {Fritzwanker, Sebastian 

Mouledous, Lionel 

Mollereau, Catherine 

Froment, Carine 

Burlet-Schiltz, Odile 

Effah, Felix 

Bailey, Alexis 

Spetea, Mariana 

Reinscheid, Rainer K 

Schulz, Stefan 

Kliewer, Andrea 

eng 

SFB/TR166-TPC5/Deutsche Forschungsgemeinschaft (German Research Foundation) 

SCHU924/18-1/Deutsche Forschungsgemeinschaft (German Research Foundation) 

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

England 

2021/09/16 

Commun Biol. 2021 Sep 14;4(1):1070. doi: 10.1038/s42003-021-02580-6.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN9o,

title = {Protein sequence comparison of human and non-human primate tooth proteomes},

author = {C. Froment and C. Zanolli and M. Hourset and E. Mouton-Barbosa and A. Moreira and O. Burlet-Schiltz and C. Mollereau},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33189847},

doi = {10.1016/j.jprot.2020.104045},

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

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {J Proteomics},

volume = {231},

pages = {104045},

abstract = {In the context of human evolution, the study of proteins may overcome the limitation of the high degradation of ancient DNA over time to provide biomolecular information useful for the phylogenetic reconstruction of hominid taxa. In this study, we used a shotgun proteomics approach to compare the tooth proteomes of extant human and non-human primates (gorilla, chimpanzee, orangutan and baboon) in order to search for a panel of peptides able to discriminate between taxa and further help reconstructing the evolutionary relationships of fossil primates. Among the 25 proteins shared by the five genera datasets, we found a combination of peptides with sequence variations allowing to differentiate the hominid taxa in the proteins AHSG, AMBN, APOA1, BGN, C9, COL11A2, COL22A1, COL3A1, DSPP, F2, LUM, OMD, PCOLCE and SERPINA1. The phylogenetic tree confirms the placement of the samples in the appropriate genus branches. Altogether, the results provide experimental evidence that a shotgun proteomics approach on dental tissue has the potential to detect taxonomic variation, which is promising for future investigations of uncharacterized and/or fossil hominid/hominin specimens. SIGNIFICANCE: A shotgun proteomics approach on human and non-human primate teeth allowed to identify peptides with taxonomic interest, highlighting the potential for future studies on hominid fossils.},

note = {Froment, Carine 

Zanolli, Clement 

Hourset, Mathilde 

Mouton-Barbosa, Emmanuelle 

Moreira, Andreia 

Burlet-Schiltz, Odile 

Mollereau, Catherine 

eng 

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

Netherlands 

2020/11/16 

J Proteomics. 2021 Jan 16;231:104045. doi: 10.1016/j.jprot.2020.104045. Epub 2020 Nov 13.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN10,

title = {Application of pulsed electric fields for the biocompatible extraction of proteins from the microalga Haematococcus pluvialis},

author = {H. Gateau and V. Blanckaert and B. Veidl and O. Burlet-Schiltz and C. Pichereaux and A. Gargaros and J. Marchand and B. Schoefs},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33147566},

doi = {10.1016/j.bioelechem.2020.107588},

issn = {1878-562X (Electronic) 1567-5394 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Bioelectrochemistry},

volume = {137},

pages = {107588},

abstract = {This study aims to employ a pulsed electric field (PEF) treatment for the biocompatible (non-destructive) extraction of proteins from living cells of the green microalga Haematococcus pluvialis. Using a field strength of 1kVcm(-1), we achieved the extraction of 10.2microg protein per mL of culture, which corresponded to 46% of the total amount of proteins that could be extracted by complete destructive extraction (i.e. the grinding of biomass with glass beads). We found that the extraction yield was not improved by stronger field strengths and was not dependent on the pulse frequency. A biocompatibility index (BI) was defined as the relative abundance of cells that remained alive after the PEF treatment. This index relied on measurements of several physiological parameters after a PEF treatment. It was found that at 1kVcm(-1) that cultures recovered after 72h. Therefore, these PEF conditions constituted a good compromise between protein extraction efficiency and culture survival. To characterize the PEF treatment further at a molecular level, mass spectrometry-based proteomics analyses of PEF-prepared extracts was used. This led to the identification of 52 electro-extracted proteins. Of these, only 16 proteins were identified when proteins were extracted with PEF at 0.5cm(-1). They belong to core metabolism, stress response and cell movement. Unassigned proteins were also extracted. Their physiological implications and possible utilization in food as alimentary complements are discussed.},

note = {Gateau, Helene 

Blanckaert, Vincent 

Veidl, Brigitte 

Burlet-Schiltz, Odile 

Pichereaux, Carole 

Gargaros, Audrey 

Marchand, Justine 

Schoefs, Benoit 

eng 

Netherlands 

2020/11/05 

Bioelectrochemistry. 2021 Feb;137:107588. doi: 10.1016/j.bioelechem.2020.107588. Epub 2020 Jul 15.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN20,

title = {ProMetIS, deep phenotyping of mouse models by combined proteomics and metabolomics analysis},

author = {A. Imbert and M. Rompais and M. Selloum and F. Castelli and E. Mouton-Barbosa and M. Brandolini-Bunlon and E. Chu-Van and C. Joly and A. Hirschler and P. Roger and T. Burger and S. Leblanc and T. Sorg and S. Ouzia and Y. Vandenbrouck and C. Medigue and C. Junot and M. Ferro and E. Pujos-Guillot and A. G. Peredo and F. Fenaille and C. Carapito and Y. Herault and E. A. Thevenot},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34862403},

doi = {10.1038/s41597-021-01095-3},

issn = {2052-4463 (Electronic) 2052-4463 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Sci Data},

volume = {8},

number = {1},

pages = {311},

abstract = {Genes are pleiotropic and getting a better knowledge of their function requires a comprehensive characterization of their mutants. Here, we generated multi-level data combining phenomic, proteomic and metabolomic acquisitions from plasma and liver tissues of two C57BL/6 N mouse models lacking the Lat (linker for activation of T cells) and the Mx2 (MX dynamin-like GTPase 2) genes, respectively. Our dataset consists of 9 assays (1 preclinical, 2 proteomics and 6 metabolomics) generated with a fully non-targeted and standardized approach. The data and processing code are publicly available in the ProMetIS R package to ensure accessibility, interoperability, and reusability. The dataset thus provides unique molecular information about the physiological role of the Lat and Mx2 genes. Furthermore, the protocols described herein can be easily extended to a larger number of individuals and tissues. Finally, this resource will be of great interest to develop new bioinformatic and biostatistic methods for multi-omics data integration.},

note = {Imbert, Alyssa 

Rompais, Magali 

Selloum, Mohammed 

Castelli, Florence 

Mouton-Barbosa, Emmanuelle 

Brandolini-Bunlon, Marion 

Chu-Van, Emeline 

Joly, Charlotte 

Hirschler, Aurelie 

Roger, Pierrick 

Burger, Thomas 

Leblanc, Sophie 

Sorg, Tania 

Ouzia, Sadia 

Vandenbrouck, Yves 

Medigue, Claudine 

Junot, Christophe 

Ferro, Myriam 

Pujos-Guillot, Estelle 

de Peredo, Anne Gonzalez 

Fenaille, Francois 

Carapito, Christine 

Herault, Yann 

Thevenot, Etienne A 

eng 

ANR-11-INBS-0013/Agence Nationale de la Recherche (French National Research Agency) 

ANR-10-INBS-0008/Agence Nationale de la Recherche (French National Research Agency) 

ANR-10-INBS-0007/Agence Nationale de la Recherche (French National Research Agency) 

ANR-11-INBS-0010/Agence Nationale de la Recherche (French National Research Agency) 

ANR-10-INBS-000/Agence Nationale de la Recherche (French National Research Agency) 

Dataset 

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

England 

2021/12/05 

Sci Data. 2021 Dec 3;8(1):311. doi: 10.1038/s41597-021-01095-3.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN11,

title = {The T cell CD6 receptor operates a multitask signalosome with opposite functions in T cell activation},

author = {D. Mori and C. Gregoire and G. Voisinne and J. Celis-Gutierrez and R. Aussel and L. Girard and M. Camus and M. Marcellin and J. Argenty and O. Burlet-Schiltz and F. Fiore and A. Gonzalez Peredo and M. Malissen and R. Roncagalli and B. Malissen},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33125054},

doi = {10.1084/jem.20201011},

issn = {1540-9538 (Electronic) 0022-1007 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {J Exp Med},

volume = {218},

number = {2},

abstract = {To determine the respective contribution of the LAT transmembrane adaptor and CD5 and CD6 transmembrane receptors to early TCR signal propagation, diversification, and termination, we describe a CRISPR/Cas9-based platform that uses primary mouse T cells and permits establishment of the composition of their LAT, CD5, and CD6 signalosomes in only 4 mo using quantitative mass spectrometry. We confirmed that positive and negative functions can be solely assigned to the LAT and CD5 signalosomes, respectively. In contrast, the TCR-inducible CD6 signalosome comprised both positive (SLP-76, ZAP70, VAV1) and negative (UBASH3A/STS-2) regulators of T cell activation. Moreover, CD6 associated independently of TCR engagement to proteins that support its implication in inflammatory pathologies necessitating T cell transendothelial migration. The multifaceted role of CD6 unveiled here accounts for past difficulties in classifying it as a coinhibitor or costimulator. Congruent with our identification of UBASH3A within the CD6 signalosome and the view that CD6 constitutes a promising target for autoimmune disease treatment, single-nucleotide polymorphisms associated with human autoimmune diseases have been found in the Cd6 and Ubash3a genes.},

note = {Mori, Daiki 

Gregoire, Claude 

Voisinne, Guillaume 

Celis-Gutierrez, Javier 

Aussel, Rudy 

Girard, Laura 

Camus, Mylene 

Marcellin, Marlene 

Argenty, Jeremy 

Burlet-Schiltz, Odile 

Fiore, Frederic 

Gonzalez de Peredo, Anne 

Malissen, Marie 

Roncagalli, Romain 

Malissen, Bernard 

eng 

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

2020/10/31 

J Exp Med. 2021 Feb 1;218(2). pii: 211516. doi: 10.1084/jem.20201011.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN12,

title = {Rv0180c contributes to Mycobacterium tuberculosis cell shape and to infectivity in mice and macrophages},

author = {D. Payros and H. Alonso and W. Malaga and A. Volle and S. Mazeres and S. Dejean and S. Valiere and F. Moreau and S. Balor and A. Stella and L. Combes-Soia and O. Burlet-Schiltz and O. Bouchez and J. Nigou and C. Astarie-Dequeker and C. Guilhot},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34724002},

doi = {10.1371/journal.ppat.1010020},

issn = {1553-7374 (Electronic) 1553-7366 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {PLoS Pathog},

volume = {17},

number = {11},

pages = {e1010020},

abstract = {Mycobacterium tuberculosis, the main causative agent of human tuberculosis, is transmitted from person to person via small droplets containing very few bacteria. Optimizing the chance to seed in the lungs is therefore a major adaptation to favor survival and dissemination in the human population. Here we used TnSeq to identify genes important for the early events leading to bacterial seeding in the lungs. Beside several genes encoding known virulence factors, we found three new candidates not previously described: rv0180c, rv1779c and rv1592c. We focused on the gene, rv0180c, of unknown function. First, we found that deletion of rv0180c in M. tuberculosis substantially reduced the initiation of infection in the lungs of mice. Next, we established that Rv0180c enhances entry into macrophages through the use of complement-receptor 3 (CR3), a major phagocytic receptor for M. tuberculosis. Silencing CR3 or blocking the CR3 lectin site abolished the difference in entry between the wild-type parental strain and the Deltarv0180c::km mutant. However, we detected no difference in the production of both CR3-known carbohydrate ligands (glucan, arabinomannan, mannan), CR3-modulating lipids (phthiocerol dimycocerosate), or proteins in the capsule of the Deltarv0180c::km mutant in comparison to the wild-type or complemented strains. By contrast, we established that Rv0180c contributes to the functionality of the bacterial cell envelope regarding resistance to toxic molecule attack and cell shape. This alteration of bacterial shape could impair the engagement of membrane receptors that M. tuberculosis uses to invade host cells, and open a new perspective on the modulation of bacterial infectivity.},

note = {Payros, Delphine 

Alonso, Henar 

Malaga, Wladimir 

Volle, Arnaud 

Mazeres, Serge 

Dejean, Sebastien 

Valiere, Sophie 

Moreau, Flavie 

Balor, Stephanie 

Stella, Alexandre 

Combes-Soia, Lucie 

Burlet-Schiltz, Odile 

Bouchez, Olivier 

Nigou, Jerome 

Astarie-Dequeker, Catherine 

Guilhot, Christophe 

eng 

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

2021/11/02 

PLoS Pathog. 2021 Nov 1;17(11):e1010020. doi: 10.1371/journal.ppat.1010020. eCollection 2021 Nov.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN25,

title = {The final step of 40S ribosomal subunit maturation is controlled by a dual key lock},

author = {L. Plassart and R. Shayan and C. Montellese and D. Rinaldi and N. Larburu and C. Pichereaux and C. Froment and S. Lebaron and M. F. O'Donohue and U. Kutay and J. Marcoux and P. E. Gleizes and C. Plisson-Chastang},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33908345},

doi = {10.7554/eLife.61254},

issn = {2050-084X (Electronic) 2050-084X (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Elife},

volume = {10},

abstract = {Preventing premature interaction of pre-ribosomes with the translation apparatus is essential for translational accuracy. Hence, the final maturation step releasing functional 40S ribosomal subunits, namely processing of the 18S ribosomal RNA 3' end, is safeguarded by the protein DIM2, which both interacts with the endoribonuclease NOB1 and masks the rRNA cleavage site. To elucidate the control mechanism that unlocks NOB1 activity, we performed cryo-electron microscopy analysis of late human pre-40S particles purified using a catalytically inactive form of the ATPase RIO1. These structures, together with in vivo and in vitro functional analyses, support a model in which ATP-loaded RIO1 cooperates with ribosomal protein RPS26/eS26 to displace DIM2 from the 18S rRNA 3' end, thereby triggering final cleavage by NOB1; release of ADP then leads to RIO1 dissociation from the 40S subunit. This dual key lock mechanism requiring RIO1 and RPS26 guarantees the precise timing of pre-40S particle conversion into translation-competent ribosomal subunits.},

note = {Plassart, Laura 

Shayan, Ramtin 

Montellese, Christian 

Rinaldi, Dana 

Larburu, Natacha 

Pichereaux, Carole 

Froment, Carine 

Lebaron, Simon 

O'Donohue, Marie-Francoise 

Kutay, Ulrike 

Marcoux, Julien 

Gleizes, Pierre-Emmanuel 

Plisson-Chastang, Celia 

eng 

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

England 

2021/04/29 

Elife. 2021 Apr 28;10. pii: 61254. doi: 10.7554/eLife.61254.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN17,

title = {Lipoprotein DolP supports proper folding of BamA in the bacterial outer membrane promoting fitness upon envelope stress},

author = {D. Ranava and Y. Yang and L. Orenday-Tapia and F. Rousset and C. Turlan and V. Morales and L. Cui and C. Moulin and C. Froment and G. Munoz and J. Rech and J. Marcoux and A. Caumont-Sarcos and C. Albenne and D. Bikard and R. Ieva},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33847565},

doi = {10.7554/eLife.67817},

issn = {2050-084X (Electronic) 2050-084X (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Elife},

volume = {10},

abstract = {In Proteobacteria, integral outer membrane proteins (OMPs) are crucial for the maintenance of the envelope permeability barrier to some antibiotics and detergents. In Enterobacteria, envelope stress caused by unfolded OMPs activates the sigmaE (sigma(E)) transcriptional response. sigma(E) upregulates OMP biogenesis factors, including the beta-barrel assembly machinery (BAM) that catalyses OMP folding. Here we report that DolP (formerly YraP), a sigma(E)-upregulated and poorly understood outer membrane lipoprotein, is crucial for fitness in cells that undergo envelope stress. We demonstrate that DolP interacts with the BAM complex by associating with outer membrane-assembled BamA. We provide evidence that DolP is important for proper folding of BamA that overaccumulates in the outer membrane, thus supporting OMP biogenesis and envelope integrity. Notably, mid-cell recruitment of DolP had been linked to regulation of septal peptidoglycan remodelling by an unknown mechanism. We now reveal that, during envelope stress, DolP loses its association with the mid-cell, thereby suggesting a mechanistic link between envelope stress caused by impaired OMP biogenesis and the regulation of a late step of cell division.},

note = {Ranava, David 

Yang, Yiying 

Orenday-Tapia, Luis 

Rousset, Francois 

Turlan, Catherine 

Morales, Violette 

Cui, Lun 

Moulin, Cyril 

Froment, Carine 

Munoz, Gladys 

Rech, Jerome 

Marcoux, Julien 

Caumont-Sarcos, Anne 

Albenne, Cecile 

Bikard, David 

Ieva, Raffaele 

eng 

ATIP-Avenir/Centre National de la Recherche Scientifique 

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

ANR-10-LABX-62-IBEID/Agence Nationale de la Recherche 

PostDoc Fellowship/Fondation pour la Recherche Medicale 

677823/ERC_/European Research Council/International 

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

England 

2021/04/14 

Elife. 2021 Apr 13;10. pii: 67817. doi: 10.7554/eLife.67817.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN24,

title = {The chaperone-like protein Cdc48 regulates ubiquitin-proteasome system in plants},

author = {C. Rosnoblet and P. Chatelain and A. Klinguer and H. Begue and P. Winckler and C. Pichereaux and D. Wendehenne},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33908641},

doi = {10.1111/pce.14073},

issn = {1365-3040 (Electronic) 0140-7791 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Plant Cell Environ},

volume = {44},

number = {8},

pages = {2636-2655},

abstract = {The degradation of misfolded proteins is mainly mediated by the ubiquitin-proteasome system (UPS). UPS can be assisted by the protein Cdc48 but the relationship between UPS and Cdc48 in plants has been poorly investigated. Here, we analysed the regulation of UPS by Cdc48 in tobacco thanks to two independent cell lines overexpressing Cdc48 constitutively and plant leaves overexpressing Cdc48 transiently. In the cell lines, the accumulation of ubiquitinated proteins was affected both quantitatively and qualitatively and the number of proteasomal subunits was modified, while proteolytic activities were unchanged. Similarly, the over-expression of Cdc48 in planta impacted the accumulation of ubiquitinated proteins. A similar process occurred in leaves overexpressing transiently Rpn3, a proteasome subunit. Cdc48 being involved in plant immunity, its regulation of UPS was also investigated in response to cryptogein, an elicitor of immune responses. In the cell lines stably overexpressing Cdc48 and in leaves transiently overexpressing Cdc48 and/or Rpn3, cryptogein triggered a premature cell death while no increase of the proteasomal activity occurred. Overall, this study highlights a role for Cdc48 in ubiquitin homeostasis and confirms its involvement, as well as that of Rpn3, in the processes underlying the hypersensitive response.},

note = {Rosnoblet, Claire 

Chatelain, Pauline 

Klinguer, Agnes 

Begue, Herve 

Winckler, Pascale 

Pichereaux, Carole 

Wendehenne, David 

eng 

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

2021/04/29 

Plant Cell Environ. 2021 Aug;44(8):2636-2655. doi: 10.1111/pce.14073. Epub 2021 Jun 2.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN23,

title = {Pharmacologic Normalization of Pancreatic Cancer-Associated Fibroblast Secretome Impairs Prometastatic Cross-Talk With Macrophages},

author = {R. Samain and A. Brunel and T. Douche and M. Fanjul and S. Cassant-Sourdy and J. Rochotte and J. Cros and C. Neuzillet and J. Raffenne and C. Duluc and A. Perraud and J. Nigri and V. Gigoux and I. Bieche and M. Ponzo and G. Carpentier and I. Cascone and R. Tomasini and H. A. Schmid and M. Mathonnet and R. Nicolle and M. P. Bousquet and Y. Martineau and S. Pyronnet and C. Jean and C. Bousquet},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33482394},

doi = {10.1016/j.jcmgh.2021.01.008},

issn = {2352-345X (Electronic) 2352-345X (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Cell Mol Gastroenterol Hepatol},

volume = {11},

number = {5},

pages = {1405-1436},

abstract = {BACKGROUND & AIMS: Cancer-associated fibroblasts (CAFs) from pancreatic adenocarcinoma (PDA) present high protein synthesis rates. CAFs express the G-protein-coupled somatostatin receptor sst1. The sst1 agonist SOM230 blocks CAF protumoral features in vitro and in immunocompromised mice. We have explored here the therapeutic potential of SOM230, and underlying mechanisms, in immunocompetent models of murine PDA mimicking the heavy fibrotic and immunosuppressive stroma observed in patient tumors. METHODS: Large-scale mass spectrometry analyses were performed on media conditioned from 9 patient PDA-derived CAF primary cultures. Spontaneous transgenic and experimental (orthotopic co-graft of tumor cells plus CAFs) PDA-bearing mice were longitudinally ultrasound-monitored for tumor and metastatic progression. Histopathology and flow cytometry analyses were performed on primary tumors and metastases. Stromal signatures were functionally validated through bioinformatics using several published, and 1 original, PDA database. RESULTS: Proteomics on the CAF secretome showed that SOM230 controls stromal activities including inflammatory responses. Among the identified secreted proteins, we validated that colony-stimulating factor 1 (CSF-1) (a macrophage growth factor) was reduced by SOM230 in the tumor and plasma of PDA-harboring mice, alongside intratumor stromal normalization (reduced CAF and macrophage activities), and dramatic metastasis reduction. In transgenic mice, these SOM230 benefits alleviate the chemotherapy-induced (gemcitabine) immunosuppressive stroma reshaping. Mechanistically, SOM230 acts in vivo on CAFs through sst1 to disrupt prometastatic CAF production of CSF-1 and cross-talk with macrophages. We found that in patients, stromal CSF-1 was associated with aggressive PDA forms. CONCLUSIONS: We propose SOM230 as an antimetastatic therapy in PDA for its capacity to remodel the fibrotic and immunosuppressive myeloid stroma. This pharmacotherapy should benefit PDA patients treated with chemotherapies.},

note = {Samain, Remi 

Brunel, Alexia 

Douche, Thibault 

Fanjul, Marjorie 

Cassant-Sourdy, Stephanie 

Rochotte, Julia 

Cros, Jerome 

Neuzillet, Cindy 

Raffenne, Jerome 

Duluc, Camille 

Perraud, Aurelie 

Nigri, Jeremy 

Gigoux, Veronique 

Bieche, Ivan 

Ponzo, Matteo 

Carpentier, Gilles 

Cascone, Ilaria 

Tomasini, Richard 

Schmid, Herbert A 

Mathonnet, Muriel 

Nicolle, Remy 

Bousquet, Marie-Pierre 

Martineau, Yvan 

Pyronnet, Stephane 

Jean, Christine 

Bousquet, Corinne 

eng 

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

2021/01/23 

Cell Mol Gastroenterol Hepatol. 2021;11(5):1405-1436. doi: 10.1016/j.jcmgh.2021.01.008. Epub 2021 Jan 20.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN14,

title = {Colitis Linked to Endoplasmic Reticulum Stress Induces Trypsin Activity Affecting Epithelial Functions},

author = {N. Sola Tapias and A. Denadai-Souza and C. Rolland-Fourcade and M. Quaranta-Nicaise and C. Blanpied and M. Marcellin and A. Edir and C. Rolland and C. Cirillo and G. Dietrich and L. Alric and G. Portier and S. Kirzin and D. Bonnet and E. Mas and O. Burlet-Schiltz and C. Deraison and C. Bonnart and N. Vergnolle and F. Barreau},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33609354},

doi = {10.1093/ecco-jcc/jjab035},

issn = {1876-4479 (Electronic) 1873-9946 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {J Crohns Colitis},

volume = {15},

number = {9},

pages = {1528-1541},

abstract = {BACKGROUND AND AIMS: Intestinal epithelial cells [IECs] from inflammatory bowel disease [IBD] patients exhibit an excessive induction of endoplasmic reticulum stress [ER stress] linked to altered intestinal barrier function and inflammation. Colonic tissues and the luminal content of IBD patients are also characterized by increased serine protease activity. The possible link between ER stress and serine protease activity in colitis-associated epithelial dysfunctions is unknown. We aimed to study the association between ER stress and serine protease activity in enterocytes and its impact on intestinal functions. METHODS: The impact of ER stress induced by Thapsigargin on serine protease secretion was studied using either human intestinal cell lines or organoids. Moreover, treating human intestinal cells with protease-activated receptor antagonists allowed us to investigate ER stress-resulting molecular mechanisms that induce proteolytic activity and alter intestinal epithelial cell biology. RESULTS: Colonic biopsies from IBD patients exhibited increased epithelial trypsin-like activity associated with elevated ER stress. Induction of ER stress in human intestinal epithelial cells displayed enhanced apical trypsin-like activity. ER stress-induced increased trypsin activity destabilized intestinal barrier function by increasing permeability and by controlling inflammatory mediators such as C-X-C chemokine ligand 8 [CXCL8]. The deleterious impact of ER stress-associated trypsin activity was specifically dependent on the activation of protease-activated receptors 2 and 4. CONCLUSIONS: Excessive ER stress in IECs caused an increased release of trypsin activity that, in turn, altered intestinal barrier function, promoting the development of inflammatory process.},

note = {Sola Tapias, Nuria 

Denadai-Souza, Alexandre 

Rolland-Fourcade, Claire 

Quaranta-Nicaise, Muriel 

Blanpied, Catherine 

Marcellin, Marlene 

Edir, Anissa 

Rolland, Corinne 

Cirillo, Carla 

Dietrich, Gilles 

Alric, Laurent 

Portier, Guillaume 

Kirzin, Sylvain 

Bonnet, Delphine 

Mas, Emmanuel 

Burlet-Schiltz, Odile 

Deraison, Celine 

Bonnart, Chrystelle 

Vergnolle, Nathalie 

Barreau, Frederick 

eng 

French Ministry of Research and Technology 

ANR JCJC-11JSV1 001 01-IBDase/National Agency for Research 

ERC- 310973 PIPE/ERC_/European Research Council/International 

ANR-11-EQPX-0003/French government 

England 

2021/02/21 

J Crohns Colitis. 2021 Sep 25;15(9):1528-1541. doi: 10.1093/ecco-jcc/jjab035.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN15,

title = {Opposing regulatory functions of the TIM3 (HAVCR2) signalosome in primary effector T cells as revealed by quantitative interactomics},

author = {Y. Zhai and J. Celis-Gutierrez and G. Voisinne and D. Mori and L. Girard and O. Burlet-Schiltz and A. G. Peredo and R. Roncagalli and B. Malissen},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33139903},

doi = {10.1038/s41423-020-00575-7},

issn = {2042-0226 (Electronic) 1672-7681 (Linking)},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Cell Mol Immunol},

volume = {18},

number = {6},

pages = {1581-1583},

note = {Zhai, Yunhao 

Celis-Gutierrez, Javier 

Voisinne, Guillaume 

Mori, Daiki 

Girard, Laura 

Burlet-Schiltz, Odile 

de Peredo, Anne Gonzalez 

Roncagalli, Romain 

Malissen, Bernard 

eng 

787300/EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 

SUPERBASILIC/Agence Nationale de la Recherche (French National Research Agency) 

ANR-11-LABEX-0043/Agence Nationale de la Recherche (French National Research Agency) 

ANR-10-IDEX-0001-02 PSL/Agence Nationale de la Recherche (French National Research Agency) 

ANR-10-INBS-08/Agence Nationale de la Recherche (French National Research Agency) 

Letter 

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

China 

2020/11/04 

Cell Mol Immunol. 2021 Jun;18(6):1581-1583. doi: 10.1038/s41423-020-00575-7. Epub 2020 Nov 2.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{felix_structural_2021,

title = {Structural and functional analysis of the Francisella lysine decarboxylase as a key actor in oxidative stress resistance},

author = {Jan Felix and Claire Siebert and Julia Novion Ducassou and Jérôme Nigou and Pierre Simon Garcia and Angélique Fraudeau and Karine Huard and Caroline Mas and Céline Brochier-Armanet and Yohann Couté and Irina Gutsche and Patricia Renesto},

url = {http://www.nature.com/articles/s41598-020-79611-5},

doi = {10.1038/s41598-020-79611-5},

issn = {2045-2322},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Scientific Reports},

volume = {11},

number = {1},

pages = {972},

abstract = {Abstract 

 

 Francisella tularensis 

 is one of the most virulent pathogenic bacteria causing the acute human respiratory disease tularemia. While the mechanisms underlying 

 F. tularensis 

 pathogenesis are largely unknown, previous studies have shown that a 

 F. novicida 

 transposon mutant with insertions in a gene coding for a putative lysine decarboxylase was attenuated in mouse spleen, suggesting a possible role of its protein product as a virulence factor. Therefore, we set out to structurally and functionally characterize the 

 F. novicida 

 lysine decarboxylase 

 , 

 which we termed LdcF 

 . 

 Here, we investigate the genetic environment of 

 ldcF 

 as well as its evolutionary relationships with other basic AAT-fold amino acid decarboxylase superfamily members, known as key actors in bacterial adaptative stress response and polyamine biosynthesis. We determine the crystal structure of LdcF and compare it with the most thoroughly studied lysine decarboxylase, 

 E. coli 

 LdcI 

 . 

 We analyze the influence of 

 ldcF 

 deletion on bacterial growth under different stress conditions in dedicated growth media, as well as in infected macrophages, and demonstrate its involvement in oxidative stress resistance. Finally, our mass spectrometry-based quantitative proteomic analysis enables identification of 80 proteins with expression levels significantly affected by 

 ldcF 

 deletion, including several DNA repair proteins potentially involved in the diminished capacity of the 

 F. novicida 

 mutant to deal with oxidative stress. Taken together, we uncover an important role of LdcF in 

 F. novicida 

 survival in host cells through participation in oxidative stress response, thereby singling out this previously uncharacterized protein as a potential drug target.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{takata-tsuji_microglia_2021,

title = {Microglia modulate gliotransmission through the regulation of VAMP2 proteins in astrocytes},

author = {Fuyuko Takata-Tsuji and Naura Chounlamountri and Le-Duy Do and Camille Philippot and Julia Novion Ducassou and Yohann Couté and Sarrah Ben Achour and Jérôme Honnorat and Christophe Place and Olivier Pascual},

doi = {10.1002/glia.23884},

issn = {1098-1136},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Glia},

volume = {69},

number = {1},

pages = {61--72},

abstract = {Vesicular release is one of the release mechanisms of various signaling molecules. In neurons, the molecular machinery involved in vesicular release has been designed through evolution to trigger fast and synchronous release of neurotransmitters. Similar machinery with a slower kinetic and a slightly different molecular assembly allows astrocytes to release various transmitters such as adenosine triphosphate (ATP), glutamate, and D-serine. Astrocytes are important modulators of neurotransmission through gliotransmitter release. We recently demonstrated that microglia, another type of glia, release ATP to modulate synaptic transmission using astrocytes as intermediate. We now report that microglia regulate astrocytic gliotransmission through the regulation of SNARE proteins in astrocytes. Indeed, we found that gliotransmission triggered by P2Y1 agonist is impaired in slices from transgenic mice devoid of microglia. Using total internal reflection fluorescence imaging, we found that the vesicular release of gliotransmitter by astrocytes was different in cultures lacking microglia compared to vesicular release in astrocytes cocultured with microglia. Quantification of the kinetic of vesicular release indicates that the overall release appears to be faster in pure astrocyte cultures with more vesicles close to the membrane when compared to astrocytes cocultured with microglia. Finally, biochemical investigation of SNARE protein expression indicates an upregulation of VAMP2 in absence of microglia. Altogether, these results indicate that microglia seems to be involved in the regulation of an astrocytic phenotype compatible with proper gliotransmission. The mechanisms described in this study could be of importance for central nervous system diseases where microglia are activated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{adrait_liquid_2021,

title = {Liquid Biopsy of Bile based on Targeted Mass Spectrometry for the Diagnosis of Malignant Biliary Strictures},

author = {Annie Adrait and Jean-Marc Dumonceau and Myriam Delhaye and Isabelle Annessi-Ramseyer and Jean-Louis Frossard and Yohann Couté and Annarita Farina},

doi = {10.1111/cts.12890},

issn = {1752-8062},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Clinical and Translational Science},

volume = {14},

number = {1},

pages = {148--152},

abstract = {Bile holds biomarkers of malignant biliary strictures (MBS) but is unsuited for automated analyzers used in routine diagnostic laboratories. Selected reaction monitoring (SRM) is a flexible high-throughput analytical approach based on targeted mass spectrometry (MS) already implemented in clinical settings. We tested the hypothesis that SRM could be used to quantify cancer biomarkers in human bile. An SRM-based assay was developed to simultaneously quantify up to 37 peptides from 13 bile proteins in a developmental cohort of 15 patients (MBS},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{van_lis_phylogenetic_2021,

title = {Phylogenetic and functional diversity of aldehyde-alcohol dehydrogenases in microalgae},

author = {Robert Lis and Yohann Couté and Sabine Brugière and Nicolas J. Tourasse and Benoist Laurent and Wolfgang Nitschke and Olivier Vallon and Ariane Atteia},

url = {http://link.springer.com/10.1007/s11103-020-01105-9},

doi = {10.1007/s11103-020-01105-9},

issn = {0167-4412, 1573-5028},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Plant Molecular Biology},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{trauchessec_innovative_2021,

title = {An innovative standard for LC-MS-based HCP-profiling and accurate quantity assessment: Application to batch consistency in viral vaccine samples},

author = {Mathieu Trauchessec and Anne Marie Hesse and Alexandra Kraut and Yves Berard and Laura Herment and Tanguy Fortin and Christophe Bruley and Myriam Ferro and Catherine Manin},

doi = {10.1002/pmic.202000152},

issn = {1615-9861},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Proteomics},

pages = {e2000152},

abstract = {Biotherapeutics, molecules produced from biological systems, require rigorous purification steps to remove impurities including host cell proteins (HCPs). Regulatory guidelines require manufacturers to monitor process-related impurities along the purification workflow. Mass spectrometry (MS) has recently been considered as a complementary method to the well-established ELISA for HCPs quantification, since it has the advantage of unambiguously identifying individual HCP. In this study, we developed an innovative standard dedicated to MS-based HCP-profiling analysis in order to monitor the consistency of viral vaccine intermediate purification samples. This standard, termed the HCP-PROFILER standard, is composed of a water-soluble bead (READYBEADSTM technology) which, after being added into the sample, releases unlabeled peptides in controlled amounts. The standard meets three desired criteria: (1) it is composed of multiple peptides, at different concentration levels, allowing construction of a calibration curve covering the dynamic range of HCPs present in the target sample, ensuring quantification accuracy; (2) it demonstrates high batch-to-batch reproducibility, ensuring quantification robustness and consistency over time; and (3) it is easy to use and avoids user-induced analytical biases. In this study, we present the use of the HCP-PROFILER standard for vaccine batches comparison and downstream process performance studies. This article is protected by copyright. All rights reserved.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rayapuram_chromatin_2021,

title = {Chromatin phosphoproteomics unravels a function for AT-hook motif nuclear localized protein AHL13 in PAMP-triggered immunity},

author = {Naganand Rayapuram and Mai Jarad and Hanna M. Alhoraibi and Jean Bigeard and Aala A. Abulfaraj and Ronny Völz and Kiruthiga Gayathri Mariappan and Marilia Almeida-Trapp and Maria Schlöffel and Emmanuelle Lastrucci and Ludovic Bonhomme and Andrea A. Gust and Axel Mithöfer and Stefan T. Arold and Delphine Pflieger and Heribert Hirt},

doi = {10.1073/pnas.2004670118},

issn = {1091-6490},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Proceedings of the National Academy of Sciences of the United States of America},

volume = {118},

number = {3},

abstract = {In many eukaryotic systems during immune responses, mitogen-activated protein kinases (MAPKs) link cytoplasmic signaling to chromatin events by targeting transcription factors, chromatin remodeling complexes, and the RNA polymerase machinery. So far, knowledge on these events is scarce in plants and no attempts have been made to focus on phosphorylation events of chromatin-associated proteins. Here we carried out chromatin phosphoproteomics upon elicitor-induced activation of Arabidopsis The events in WT were compared with those in mpk3, mpk4, and mpk6 mutant plants to decipher specific MAPK targets. Our study highlights distinct signaling networks involving MPK3, MPK4, and MPK6 in chromatin organization and modification, as well as in RNA transcription and processing. Among the chromatin targets, we characterized the AT-hook motif containing nuclear localized (AHL) DNA-binding protein AHL13 as a substrate of immune MAPKs. AHL13 knockout mutant plants are compromised in pathogen-associated molecular pattern (PAMP)-induced reactive oxygen species production, expression of defense genes, and PAMP-triggered immunity. Transcriptome analysis revealed that AHL13 regulates key factors of jasmonic acid biosynthesis and signaling and affects immunity toward Pseudomonas syringae and Botrytis cinerea pathogens. Mutational analysis of the phosphorylation sites of AHL13 demonstrated that phosphorylation regulates AHL13 protein stability and thereby its immune functions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{gilquin_peps_2021,

title = {PepS: An Innovative Microfluidic Device for Bedside Whole Blood Processing before Plasma Proteomics Analyses},

author = {Benoit Gilquin and Myriam Cubizolles and Remco Den Dulk and Frédéric Revol-Cavalier and Manuel Alessio and Charles-Elie Goujon and Camille Echampard and Gorka Arrizabalaga and Annie Adrait and Mathilde Louwagie and Patricia Laurent and Fabrice P. Navarro and Yohann Couté and Marie-Line Cosnier and Virginie Brun},

doi = {10.1021/acs.analchem.0c02270},

issn = {1520-6882},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Analytical Chemistry},

volume = {93},

number = {2},

pages = {683--690},

abstract = {Immunoassays have been used for decades in clinical laboratories to quantify proteins in serum and plasma samples. However, their limitations make them inappropriate in some cases. Recently, mass spectrometry (MS) based proteomics analysis has emerged as a promising alternative method when seeking to assess panels of protein biomarkers with a view to providing protein profiles to monitor health status. Up to now, however, translation of MS-based proteomics to the clinic has been hampered by its complexity and the substantial time and human resources necessary for sample preparation. Plasma matrix is particularly tricky to process as it contains more than 3000 proteins with concentrations spanning an extreme dynamic range (1010). To address this preanalytical challenge, we designed a microfluidic device (PepS) automating and accelerating blood sample preparation for bottom-up MS-based proteomics analysis. The microfluidic cartridge is operated through a dedicated compact instrument providing fully automated fluid processing and thermal control. In less than 2 h, the PepS device allows bedside plasma separation from whole blood, volume metering, depletion of albumin, protein digestion with trypsin, and stabilization of tryptic peptides on solid-phase extraction sorbent. For this first presentation, the performance of the PepS device was assessed using discovery proteomics and targeted proteomics, detecting a panel of three protein biomarkers routinely assayed in clinical laboratories (alanine aminotransferase 1, C-reactive protein, and myoglobin). This innovative microfluidic device and its associated instrumentation should help to streamline and simplify clinical proteomics studies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kerjouan_control_2021,

title = {Control of SRC molecular dynamics encodes distinct cytoskeletal responses by specifying signaling pathway usage},

author = {Adèle Kerjouan and Cyril Boyault and Christiane Oddou and Edwige Hiriart-Bryant and Alexei Grichine and Alexandra Kraut and Mylène Pezet and Martial Balland and Eva Faurobert and Isabelle Bonnet and Yohann Couté and Bertrand Fourcade and Corinne Albiges-Rizo and Olivier Destaing},

doi = {10.1242/jcs.254599},

issn = {1477-9137},

year  = {2021},

date = {2021-01-01},

urldate = {2021-01-01},

journal = {Journal of Cell Science},

volume = {134},

number = {2},

abstract = {Upon activation by different transmembrane receptors, the same signaling protein can induce distinct cellular responses. A way to decipher the mechanisms of such pleiotropic signaling activity is to directly manipulate the decision-making activity that supports the selection between distinct cellular responses. We developed an optogenetic probe (optoSRC) to control SRC signaling, an example of a pleiotropic signaling node, and we demonstrated its ability to generate different acto-adhesive structures (lamellipodia or invadosomes) upon distinct spatio-temporal control of SRC kinase activity. The occurrence of each acto-adhesive structure was simply dictated by the dynamics of optoSRC nanoclusters in adhesive sites, which were dependent on the SH3 and Unique domains of the protein. The different decision-making events regulated by optoSRC dynamics induced distinct downstream signaling pathways, which we characterized using time-resolved proteomic and network analyses. Collectively, by manipulating the molecular mobility of SRC kinase activity, these experiments reveal the pleiotropy-encoding mechanism of SRC signaling.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mori2021,

title = {The T cell CD6 receptor operates a multitask signalosome with opposite functions in T cell activation.},

author = {Daiki Mori and Claude Grégoire and Guillaume Voisinne and Javier Celis-Gutierrez and Rudy Aussel and Laura Girard and Mylène Camus and Marlène Marcellin and Jérémy Argenty and Odile Burlet-Schiltz and Frédéric Fiore and Anne Peredo and Marie Malissen and Romain Roncagalli and Bernard Malissen},

doi = {10.1084/jem.20201011},

year  = {2021},

date = {2021-01-01},

journal = {The Journal of experimental medicine},

volume = {218},

number = {2},

abstract = {To determine the respective contribution of the LAT transmembrane adaptor and CD5 and CD6 transmembrane receptors to early TCR signal propagation, diversification, and termination, we describe a CRISPR/Cas9-based platform that uses primary mouse T cells and permits establishment of the composition of their LAT, CD5, and CD6 signalosomes in only 4 mo using quantitative mass spectrometry. We confirmed that positive and negative functions can be solely assigned to the LAT and CD5 signalosomes, respectively. In contrast, the TCR-inducible CD6 signalosome comprised both positive (SLP-76, ZAP70, VAV1) and negative (UBASH3A/STS-2) regulators of T cell activation. Moreover, CD6 associated independently of TCR engagement to proteins that support its implication in inflammatory pathologies necessitating T cell transendothelial migration. The multifaceted role of CD6 unveiled here accounts for past difficulties in classifying it as a coinhibitor or costimulator. Congruent with our identification of UBASH3A within the CD6 signalosome and the view that CD6 constitutes a promising target for autoimmune disease treatment, single-nucleotide polymorphisms associated with human autoimmune diseases have been found in the Cd6 and Ubash3a genes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1667,

title = {ProMetIS, deep phenotyping of mouse models by combined proteomics and metabolomics analysis},

author = {A. Imbert and M. Rompais and M. Selloum and F. Castelli and E. Mouton-Barbosa and M. Brandolini-Bunlon and E. Chu-Van and C. Joly and A. Hirschler and P. Roger and T. Burger and S. Leblanc and T. Sorg and S. Ouzia and Y. Vandenbrouck and C. Medigue and C. Junot and M. Ferro and E. Pujos-Guillot and A. G. Peredo and F. Fenaille and C. Carapito and Y. Herault and E. A. Thevenot},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34862403},

doi = {10.1038/s41597-021-01095-3},

issn = {2052-4463 (Electronic) 

2052-4463 (Linking)},

year  = {2021},

date = {2021-01-01},

journal = {Sci Data},

volume = {8},

number = {1},

pages = {311},

abstract = {Genes are pleiotropic and getting a better knowledge of their function requires a comprehensive characterization of their mutants. Here, we generated multi-level data combining phenomic, proteomic and metabolomic acquisitions from plasma and liver tissues of two C57BL/6 N mouse models lacking the Lat (linker for activation of T cells) and the Mx2 (MX dynamin-like GTPase 2) genes, respectively. Our dataset consists of 9 assays (1 preclinical, 2 proteomics and 6 metabolomics) generated with a fully non-targeted and standardized approach. The data and processing code are publicly available in the ProMetIS R package to ensure accessibility, interoperability, and reusability. The dataset thus provides unique molecular information about the physiological role of the Lat and Mx2 genes. Furthermore, the protocols described herein can be easily extended to a larger number of individuals and tissues. Finally, this resource will be of great interest to develop new bioinformatic and biostatistic methods for multi-omics data integration.},

note = {2018-23},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1658,

title = {A spatial vascular transcriptomic, proteomic, and phosphoproteomic atlas unveils an angiocrine Tie-Wnt signaling axis in the liver},

author = {D. Inverso and J. Shi and K. H. Lee and M. Jakab and S. Ben-Moshe and S. R. Kulkarni and M. Schneider and G. Wang and M. Komeili and P. A. Velez and M. Riedel and C. Spegg and T. Ruppert and C. Schaeffer-Reiss and D. Helm and I. Singh and M. Boutros and S. Chintharlapalli and M. Heikenwalder and S. Itzkovitz and H. G. Augustin},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34038707},

doi = {10.1016/j.devcel.2021.05.001},

issn = {1878-1551 (Electronic) 

1534-5807 (Linking)},

year  = {2021},

date = {2021-01-01},

journal = {Dev Cell},

volume = {56},

number = {11},

pages = {1677-1693 e10},

abstract = {Single-cell transcriptomics (scRNA-seq) has revolutionized the understanding of the spatial architecture of tissue structure and function. Advancing the "transcript-centric" view of scRNA-seq analyses is presently restricted by the limited resolution of proteomics and genome-wide techniques to analyze post-translational modifications. Here, by combining spatial cell sorting with transcriptomics and quantitative proteomics/phosphoproteomics, we established the spatially resolved proteome landscape of the liver endothelium, yielding deep mechanistic insight into zonated vascular signaling mechanisms. Phosphorylation of receptor tyrosine kinases was detected preferentially in the central vein area, resulting in an atypical enrichment of tyrosine phosphorylation. Prototypic biological validation identified Tie receptor signaling as a selective and specific regulator of vascular Wnt activity orchestrating angiocrine signaling, thereby controlling hepatocyte function during liver regeneration. Taken together, the study has yielded fundamental insight into the spatial organization of liver endothelial cell signaling. Spatial sorting may be employed as a universally adaptable strategy for multiomic analyses of scRNA-seq-defined cellular (sub)-populations.},

note = {pas de projet},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1659,

title = {Vancomycin-decorated microbubbles as a theranostic agent for Staphylococcus aureus biofilms},

author = {J. J. P. Kouijzer and K. R. Lattwein and I. Beekers and S. A. G. Langeveld and M. Leon-Grooters and J. M. Strub and E. Oliva and G. L. A. Mislin and N. Jong and A. F. W. Steen and A. L. Klibanov and W. J. B. Wamel and K. Kooiman},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34624449},

doi = {10.1016/j.ijpharm.2021.121154},

issn = {1873-3476 (Electronic) 

0378-5173 (Linking)},

year  = {2021},

date = {2021-01-01},

journal = {Int J Pharm},

volume = {609},

pages = {121154},

abstract = {Bacterial biofilms are a huge burden on our healthcare systems worldwide. The lack of specificity in diagnostic and treatment possibilities result in difficult-to-treat and persistent infections. The aim of this in vitro study was to investigate if microbubbles targeted specifically to bacteria in biofilms could be used both for diagnosis as well for sonobactericide treatment and demonstrate their theranostic potential for biofilm infection management. The antibiotic vancomycin was chemically coupled to the lipid shell of microbubbles and validated using mass spectrometry and high-axial resolution 4Pi confocal microscopy. Theranostic proof-of-principle was investigated by demonstrating the specific binding of vancomycin-decorated microbubbles (vMB) to statically and flow grown Staphylococcus aureus (S. aureus) biofilms under increasing shear stress flow conditions (0-12 dyn/cm(2)), as well as confirmation of microbubble oscillation and biofilm disruption upon ultrasound exposure (2 MHz, 250 kPa, and 5,000 or 10,000 cycles) during flow shear stress of 5 dyn/cm(2) using time-lapse confocal microscopy combined with the Brandaris 128 ultra-high-speed camera. Vancomycin was successfully incorporated into the microbubble lipid shell. vMB bound significantly more often than control microbubbles to biofilms, also in the presence of free vancomycin (up to 1000 microg/mL) and remained bound under increasing shear stress flow conditions (up to 12 dyn/cm(2)). Upon ultrasound insonification biofilm area was reduced of up to 28%, as confirmed by confocal microscopy. Our results confirm the successful production of vMB and support their potential as a new theranostic tool for S. aureus biofilm infections by allowing for specific bacterial detection and biofilm disruption.},

note = {2021-02 (service chimie)},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1655,

title = {Comparative Study of Secreted Proteins, Enzymatic Activities of Wood Degradation and Stilbene Metabolization in Grapevine Botryosphaeria Dieback Fungi},

author = {C. Labois and E. Stempien and J. Schneider and C. Schaeffer-Reiss and C. Bertsch and M. L. Goddard and J. Chong},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34356948},

doi = {10.3390/jof7070568},

issn = {2309-608X (Electronic) 

2309-608X (Linking)},

year  = {2021},

date = {2021-01-01},

journal = {J Fungi (Basel)},

volume = {7},

number = {7},

abstract = {Botryosphaeriaceae fungi are plant pathogens associated with Botryosphaeria dieback. To better understand the virulence factors of these fungi, we investigated the diversity of secreted proteins and extracellular enzyme activities involved in wood degradation and stilbene metabolization in Neofusicoccumparvum and Diplodiaseriata, which are two major fungi associated with grapevine B. dieback. Regarding the analysis of proteins secreted by the two fungi, our study revealed that N. parvum, known to be more aggressive than D. seriata, was characterized by a higher quantity and diversity of secreted proteins, especially hydrolases and oxidoreductases that are likely involved in cell wall and lignin degradation. In addition, when fungi were grown with wood powder, the extracellular laccase and Mn peroxidase enzyme activities were significantly higher in D. seriata compared to N.parvum. Importantly, our work also showed that secreted Botryosphaeriaceae proteins produced after grapevine wood addition are able to rapidly metabolize the grapevine stilbenes. Overall, a higher diversity of resveratrol and piceatannol metabolization products was found with enzymes of N. parvum compared to D. seriata. This study emphasizes the diversity of secreted virulence factors found in B. dieback fungi and suggests that some resveratrol oligomers produced in grapevine wood after pathogen attack could be formed via pathogenic fungal oxidases.},

note = {2018/08},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1606,

title = {Precise Alkoxyamine Design to Enable Automated Tandem Mass Spectrometry Sequencing of Digital Poly(phosphodiester)s},

author = {K. Launay and J. A. Amalian and E. Laurent and L. Oswald and A. Al Ouahabi and A. Burel and F. Dufour and C. Carapito and J. L. Clement and J. F. Lutz and L. Charles and D. Gigmes},

url = {https://www.ncbi.nlm.nih.gov/pubmed/32964618},

doi = {10.1002/anie.202010171},

issn = {1521-3773 (Electronic) 

1433-7851 (Linking)},

year  = {2021},

date = {2021-01-01},

journal = {Angew Chem Int Ed Engl},

volume = {60},

number = {2},

pages = {917-926},

abstract = {A major step towards reliable reading of information coded in the sequence of long poly(phosphodiester)s was previously achieved by introducing an alkoxyamine spacer between information sub-segments. However, MS/MS decoding had to be performed manually to safely identify useful fragments of low abundance compared to side-products from the amide-based alkoxyamine used. Here, alternative alkoxyamines were designed to prevent side-reactions and enable automated MS/MS sequencing. Different styryl-TEMPO spacers were prepared to increase radical delocalization and stiffness of the structure. Their dissociation behavior was investigated by EPR and best results were obtained with spacers containing in-chain benzyl ring, with no side-reaction during synthesis or sequencing. Automated decoding of these polymers was performed using the MS-DECODER software, which interprets fragmentation data recorded for each sub-segment and re-align them in their original order based on location tags.},

note = {pas de numéro de projet},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1592,

title = {Non-specific interactions of antibody-oligonucleotide conjugates with living cells},

author = {V. Lehot and I. Kuhn and M. Nothisen and S. Erb and S. Kolodych and S. Cianferani and G. Chaubet and A. Wagner},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33723336},

doi = {10.1038/s41598-021-85352-w},

issn = {2045-2322 (Electronic) 

2045-2322 (Linking)},

year  = {2021},

date = {2021-01-01},

journal = {Sci Rep},

volume = {11},

number = {1},

pages = {5881},

abstract = {Antibody-Oligonucleotide Conjugates (AOCs) represent an emerging class of functionalized antibodies that have already been used in a wide variety of applications. While the impact of dye and drug conjugation on antibodies' ability to bind their target has been extensively studied, little is known about the effect caused by the conjugation of hydrophilic and charged payloads such as oligonucleotides on the functions of an antibody. Previous observations of non-specific interactions of nucleic acids with untargeted cells prompted us to further investigate their impact on AOC binding abilities and cell selectivity. We synthesized a series of single- and double-stranded AOCs, as well as a human serum albumin-oligonucleotide conjugate, and studied their interactions with both targeted and non-targeted living cells using a time-resolved analysis of ligand binding assay. Our results indicate that conjugation of single strand oligonucleotides to proteins induce consistent non-specific interactions with cell surfaces while double strand oligonucleotides have little or no effect, depending on the preparation method.},

note = {2020/04},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1594,

title = {Structural studies of RNase M5 reveal two-metal-ion supported two-step dsRNA cleavage for 5S rRNA maturation},

author = {S. Oerum and M. Catala and M. Bourguet and L. Gilet and P. Barraud and S. Cianferani and C. Condon and C. Tisne},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33541205},

doi = {10.1080/15476286.2021.1885896},

issn = {1555-8584 (Electronic) 

1547-6286 (Linking)},

year  = {2021},

date = {2021-01-01},

journal = {RNA Biol},

pages = {1-11},

abstract = {All species transcribe ribosomal RNA in an immature form that requires several enzymes for processing into mature rRNA. The number and types of enzymes utilized for these processes vary greatly between different species. In low G + C Gram-positive bacteria including Bacillus subtilis and Geobacillus stearothermophilus, the endoribonuclease (RNase) M5 performs the final step in 5S rRNA maturation, by removing the 3'- and 5'-extensions from precursor (pre) 5S rRNA. This cleavage activity requires initial complex formation between the pre-rRNA and a ribosomal protein, uL18, making the full M5 substrate a ribonucleoprotein particle (RNP). M5 contains a catalytic N-terminal Toprim domain and an RNA-binding C-terminal domain, respectively, shown to assist in processing and binding of the RNP. Here, we present structural data that show how two Mg(2+) ions are accommodated in the active site pocket of the catalytic Toprim domain and investigate the importance of these ions for catalysis. We further perform solution studies that support the previously proposed 3'-before-5' order of removal of the pre-5S rRNA extensions and map the corresponding M5 structural rearrangements during catalysis.},

note = {2018/06},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1613,

title = {Iron Stearate Structures: An Original Tool for Nanoparticles Design},

author = {F. Perton and G. Cotin and C. Kiefer and J. M. Strub and S. Cianferani and J. M. Greneche and N. Parizel and B. Heinrich and B. Pichon and D. Mertz and S. Begin-Colin},

url = {https://www.ncbi.nlm.nih.gov/pubmed/34339179},

doi = {10.1021/acs.inorgchem.1c01689},

issn = {1520-510X (Electronic) 

0020-1669 (Linking)},

year  = {2021},

date = {2021-01-01},

journal = {Inorg Chem},

volume = {60},

number = {16},

pages = {12445-12456},

abstract = {Iron carboxylates are widely used as iron precursors in the thermal decomposition process or considered as in situ formed intermediate precursors. Their molecular and three-dimensional (3D)-structural nature has been shown to affect the shape, size, and composition of the resulting iron oxide nanoparticles (NPs). Among carboxylate precursors, stearates are particularly attractive because of their higher stability to aging and hydration and they are used as additives in many applications. Despite the huge interest of iron stearates, very few studies aimed up to now at deciphering their full metal-ligand structures and the mechanisms allowing us to achieve in a controlled manner the bottom-up NP formation. In this work, we have thus investigated the molecular structure and composition of two iron stearate precursors, synthesized by introducing either two (FeSt2) or three (FeSt3) stearate (St) chains. Interestingly, both iron stearates consist of lamellar structures with planes of iron polynuclear complexes (polycations) separated with stearate chains in all-trans conformation. The iron content in polycations was found very different between both iron stearates. Their detailed characterizations indicate that FeSt2 is mainly composed of [Fe3-(mu3-O)St6.xH2O]Cl, with no (or few) free stearate, whereas FeSt3 is a mixture of mainly [Fe7(mu3-O(H))6(mu2-OH)xSt12-2x]St with some [Fe3(mu3-O)St6.xH2O]St and free stearic acid. The formation of bigger polynuclear complexes with FeSt3 was related to higher hydrolysis and condensation rates within the iron(III) chloride solution compared to the iron(II) chloride solution. These data suggested a nucleation mechanism based on the condensation of polycation radicals generated by the catalytic departure of two stearate chains from an iron polycation-based molecule.},

note = {2021/02},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1617,

title = {Proteo3Dnet: a web server for the integration of structural information with interactomics data},

author = {G. Postic and J. Andreani and J. Marcoux and V. Reys and R. Guerois and J. Rey and E. Mouton-Barbosa and Y. Vandenbrouck and S. Cianferani and O. Burlet-Schiltz and G. Labesse and P. Tuffery},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33963857},

doi = {10.1093/nar/gkab332},

issn = {1362-4962 (Electronic) 

0305-1048 (Linking)},

year  = {2021},

date = {2021-01-01},

journal = {Nucleic Acids Res},

volume = {49},

number = {W1},

pages = {W567-W572},

abstract = {Proteo3Dnet is a web server dedicated to the analysis of mass spectrometry interactomics experiments. Given a flat list of proteins, its aim is to organize it in terms of structural interactions to provide a clearer overview of the data. This is achieved using three means: (i) the search for interologs with resolved structure available in the protein data bank, including cross-species remote homology search, (ii) the search for possibly weaker interactions mediated through Short Linear Motifs as predicted by ELM-a unique feature of Proteo3Dnet, (iii) the search for protein-protein interactions physically validated in the BioGRID database. The server then compiles this information and returns a graph of the identified interactions and details about the different searches. The graph can be interactively explored to understand the way the core complexes identified could interact. It can also suggest undetected partners to the experimentalists, or specific cases of conditionally exclusive binding. The interest of Proteo3Dnet, previously demonstrated for the difficult cases of the proteasome and pragmin complexes data is, here, illustrated in the context of yeast precursors to the small ribosomal subunits and the smaller interactome of 14-3-3zeta frequent interactors. The Proteo3Dnet web server is accessible at http://bioserv.rpbs.univ-paris-diderot.fr/services/Proteo3Dnet/.},

note = {pas de numero de projet - projet inter-infrastructures/bioinfo},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RN1598,

title = {Optimized Sample Preparation and Data Processing of Data-Independent Acquisition Methods for the Robust Quantification of Trace-Level Host Cell Protein Impurities in Antibody Drug Products},

author = {N. Pythoud and J. Bons and G. Mijola and A. Beck and S. Cianferani and C. Carapito},

url = {https://www.ncbi.nlm.nih.gov/pubmed/33016074},

doi = {10.1021/acs.jproteome.0c00664},

issn = {1535-3907 (Electronic) 

1535-3893 (Linking)},

year  = {2021},

date = {2021-01-01},

journal = {J Proteome Res},

volume = {20},

number = {1},

pages = {923-931},

abstract = {Host cell proteins (HCPs) are a major class of bioprocess-related impurities generated by the host organism and are generally present at low levels in purified biopharmaceutical products. The monitoring of these impurities is identified as an important critical quality attribute of monoclonal antibody (mAb) formulations not only due to the potential risk for the product stability and efficacy but also concerns linked to the immunogenicity of some of them. While overall HCP levels are usually monitored by enzyme-linked immunosorbent assay (ELISA), mass spectrometry (MS)-based approaches have been emerging as powerful and promising alternatives providing qualitative and quantitative information. However, a major challenge for liquid chromatography (LC)-MS-based methods is to deal with the wide dynamic range of drug products and the extreme sensitivity required to detect trace-level HCPs. In this study, we developed powerful and reproducible MS-based analytical workflows coupling optimized and efficient sample preparations, the library-free data-independent acquisition (DIA) method, and stringent validation criteria. The performances of several preparation protocols and DIA versus classical data-dependent acquisition (DDA) were evaluated using a series of four commercially available drug products. Depending on the selected protocols, the user has access to different information: on the one hand, a deep profiling of tens of identified HCPs and on the other hand, accurate and reproducible (coefficients of variation (CVs) < 12%) quantification of major HCPs. Overall, a final global HCP amount of a few tens of ng/mg mAb in these mAb samples was measured, while reaching a sensitivity down to the sub-ng/mg mAb level. Thus, this straightforward and robust approach can be intended as a routine quality control for any drug product analysis.},

note = {2019/15},

keywords = {},

pubstate = {published},

tppubtype = {article}

}