@article{revel_identification_2025,

title = {Identification of uranyl-binding proteins in Arabidopsis thaliana cells exposed to uranium: Insights from a metalloproteomic analysis and characterization of Glycine-Rich RNA-binding protein 7 (GRP7)},

author = {Benoît H. Revel and Adrien Favier and Jacqueline Martin-Laffon and Alicia Vallet and Jonathan Przybyla-Toscano and Sabine Brugière and Yohann Couté and Hélène Diemer and Sarah Cianférani and Thierry Rabilloud and Jacques Bourguignon and Bernhard Brutscher and Stéphane Ravanel and Claude Alban},

url = {https://linkinghub.elsevier.com/retrieve/pii/S0304389425020795},

doi = {10.1016/j.jhazmat.2025.139163},

issn = {0304-3894},

year  = {2025},

date = {2025-09-01},

urldate = {2025-07-18},

journal = {Journal of Hazardous Materials},

volume = {495},

pages = {139163},

note = {841},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{armengaud_novel_2025,

title = {Novel model organisms and proteomics for a better biological understanding},

author = {Jean Armengaud and Tristan Cardon and Susana Cristobal and Sabine Matallana-Surget and Fabrice Bertile},

url = {https://linkinghub.elsevier.com/retrieve/pii/S1874391925000685},

doi = {10.1016/j.jprot.2025.105441},

issn = {18743919},

year  = {2025},

date = {2025-05-01},

urldate = {2025-06-18},

journal = {Journal of Proteomics},

volume = {316},

pages = {105441},

abstract = {The concept of « model organisms » is being revisited in the light of the latest advances in multi-omics technologies that can now capture the full range of molecular events that occur over time, regardless of the organism studied. Classic, well-studied models, such as Escherichia coli, Saccharomyces cerevisiae, to name a few, have long been valuable for hypothesis testing, reproducibility, and sharing common platforms among researchers. However, they are not suitable for all types of research. The complexity of unanswered questions in biology demands more elaborated systems, particularly to study plant and animal biodiversity, microbial ecosystems and their interactions with their hosts if any. More integrated systems, known as « holobionts », are emerging to describe and unify host organisms and associated microorganisms, providing an overview of all their possible interactions and trajectories. Comparative evolutionary proteomics offers interesting prospects for extrapolating knowledge from a few selected model organisms to others. This approach enables a deeper characterization of the diversity of proteins and proteoforms across the three branches of the tree of life, i.e. Bacteria, Archaea, and Eukarya. It also provides a powerful means to address remaining biological questions, such as identifying the key molecular players in organisms when they are confronted to environmental challenges, like anthropogenic toxicants, pathogens, dietary shifts or climate stressors, and proposing long-term sustainable solutions.},

note = {829},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{delalande_holdup_2025,

title = {Holdup Multiplex Assay for High-Throughput Measurement of Protein–Ligand Affinity Constants Using a Mass Spectrometry Readout},

author = {François Delalande and So̷ren Østergaard and Gergo Gogl and Alexandra Cousido-Siah and Alastair G. McEwen and Yushi Men and Farida Salimova and Aurélien Rohrbacher and Camille Kostmann and Yves Nominé and Renaud Vincentelli and Pascal Eberling and Christine Carapito and Gilles Travé and Elodie Monsellier},

url = {https://doi.org/10.1021/jacs.4c11102},

doi = {10.1021/jacs.4c11102},

issn = {0002-7863},

year  = {2025},

date = {2025-04-01},

urldate = {2025-06-18},

journal = {Journal of the American Chemical Society},

volume = {147},

number = {13},

pages = {10886–10902},

abstract = {The accurate description and subsequent modeling of protein interactomes require quantification of their affinities at the proteome-wide scale. Here we develop and validate the Holdup Multiplex, a versatile assay with a mass spectrometry (MS) readout for profiling the affinities of a protein for large pools of peptides. The method can precisely quantify, in one single run, thousands of affinity constants over several orders of magnitude. The throughput, dynamic range, and sensitivity can be pushed to the performance limit of the MS readout. We applied the Holdup Multiplex to quantify in a few sample runs the affinities of the 14–3–3s, phosphoreader proteins highly abundant in humans, for 1000 different phosphopeptides. The seven human 14–3–3 isoforms were found to display similar specificities but staggered affinities, with 14–3–3γ being always the best binder and 14–3–3ε and σ being the weakest. Hundreds of new 14–3–3 binding sites were identified. We also identified dozens of 14–3–3 binding sites, some intervening in key signaling pathways, that were either stabilized or destabilized by the phytotoxin Fusicoccin-A. The results were corroborated by X-ray crystallography. Finally, we demonstrated the transferability of the Holdup Multiplex by quantifying the interactions of a PDZ domain for 5400 PBM peptides at once. The approach is applicable to any category of protein-binding ligands that can be quantifiable by mass spectrometry.},

note = {839},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{jerabkova-roda_peripheral_2025,

title = {Peripheral positioning of lysosomes supports melanoma aggressiveness},

author = {Katerina Jerabkova-Roda and Marina Peralta and Kuang-Jing Huang and Antoine Mousson and Clara Bourgeat Maudru and Louis Bochler and Ignacio Busnelli and Rabia Karali and Hélène Justiniano and Lucian-Mihai Lisii and Philippe Carl and Vincent Mittelheisser and Nandini Asokan and Annabel Larnicol and Olivier Lefebvre and Hugo Lachuer and Angélique Pichot and Tristan Stemmelen and Anne Molitor and Léa Scheid and Quentin Frenger and Frédéric Gros and Aurélie Hirschler and François Delalande and Emilie Sick and Raphaël Carapito and Christine Carapito and Dan Lipsker and Kristine Schauer and Philippe Rondé and Vincent Hyenne and Jacky G. Goetz},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982396/},

doi = {10.1038/s41467-025-58528-5},

issn = {2041-1723},

year  = {2025},

date = {2025-04-01},

urldate = {2025-06-18},

journal = {Nature Communications},

volume = {16},

pages = {3375},

abstract = {Emerging evidence suggests that the function and position of organelles are pivotal for tumor cell dissemination. Among them, lysosomes stand out as they integrate metabolic sensing with gene regulation and secretion of proteases. Yet, how their function is linked to their position and how this controls metastasis remains elusive. Here, we analyze lysosome subcellular distribution in patient-derived melanoma cells and patient biopsies and show that lysosome spreading scales with melanoma aggressiveness. Peripheral lysosomes promote matrix degradation and cell invasion which is directly linked to the lysosomal and cell transcriptional programs. Using chemo-genetical control of lysosome positioning, we demonstrate that perinuclear clustering impairs lysosome secretion, matrix degradation and invasion. Impairing lysosome spreading significantly reduces invasive outgrowth in two in vivo models, mouse and zebrafish. Our study provides a direct demonstration that lysosome positioning controls cell invasion, illustrating the importance of organelle adaptation in carcinogenesis and suggesting its potential utility for diagnosis of metastatic melanoma., The function and position of organelles are pivotal for tumor cell dissemination. Here the authors use melanoma patient samples and animal models to show that peripheral localization of lysosomes promotes metastasis by favoring lysosome exocytosis and cell invasion.},

note = {836},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{charlanne_ready_2025,

title = {Ready to dive? Early constraints help juvenile southern elephant seals (Mirounga leonina) acclimatize to aquatic life},

author = {Laura Charlanne and Fabrice Bertile and Alexandre Geffroy and Lea Hippauf and Isabelle Chery and Sandrine Zahn and Christophe Guinet and Erwan Piot and Jérome Badaut and André Ancel and Caroline Gilbert and Audrey Bergouignan},

url = {https://doi.org/10.1242/jeb.249813},

doi = {10.1242/jeb.249813},

issn = {0022-0949},

year  = {2025},

date = {2025-03-01},

urldate = {2025-06-18},

journal = {Journal of Experimental Biology},

volume = {228},

number = {6},

pages = {jeb249813},

abstract = {Breath-holding foraging implies different adaptations to limit oxygen (O2) depletion and maximize foraging time. Physiological adjustments can be mediated through O2 consumption, driven by muscle mitochondria, which can also produce reactive oxygen species during reoxygenation. Southern elephant seals spend months foraging at sea, diving for up to 1 h. Pups transition abruptly to aquatic life after a post-weaning period, during which they fast and progressively increase their activity, making this period critical for the development of an adaptive response to oxygen restriction and oxidative stress. We compared the functional capacity of a swimming muscle in 5 recently weaned and 6 adult female southern elephant seals. High-resolution respirometry was employed to examine muscle mitochondrial respiratory capacity and differences in protein and gene expression of the main regulatory pathways were determined using LC-MS/MS and RT-qPCR, respectively. Oxidative damage was measured in the plasma. We found that juveniles have higher mitochondrial coupling efficiency compared with adults, probably as a response to growth and significant physical activity reported during the post-weaning period. There were no differences in oxidative damage, but adults had a higher level of antioxidant defenses. Both hypoxia and oxidative response pathways appeared less activated in juveniles. This study highlights the differences in muscle metabolism and the likely adaptive response to hypoxia and oxidative stress between juvenile and adult south elephant seals. It also suggests that early constraints such as fasting, physical activity and short-term low O2 partial pressure exposure could contribute to immediate and long-term responses and help to acclimatize juveniles to aquatic life.},

note = {840},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ingelson-filpula_role_2025,

title = {The role of microRNA in the regulation of hepatic metabolism and energy-expensive processes in the hibernating dormouse},

author = {W. Aline Ingelson-Filpula and Anna Kübber-Heiss and Johanna Painer and Gabrielle Stalder and Hanane Hadj-Moussa and Fabrice Bertile and Caroline Habold and Sylvain Giroud and Kenneth B. Storey},

url = {https://linkinghub.elsevier.com/retrieve/pii/S0011224024003468},

doi = {10.1016/j.cryobiol.2024.105191},

issn = {00112240},

year  = {2025},

date = {2025-03-01},

urldate = {2025-01-06},

journal = {Cryobiology},

volume = {118},

pages = {105191},

abstract = {The garden dormouse (Eliomys quercinus) is a fat-storing mammal that undergoes annual periods of hibernation to mitigate the effects of food scarcity, low ambient temperatures, and reduced photoperiod that characterize winter. Like other hibernating species, this animal suppresses its metabolic rate by downregulating nonessential genes and processes in order to prolong available energy stores and limit waste accumulation throughout the season. MicroRNAs (miRNAs) are short, single-stranded, noncoding RNAs that bind to mRNA and mediate posttranscriptional suppression, making miRNA ideal for modulating widespread changes in gene expression, including global downregulation typified by metabolic rate depression. Using next-generation sequencing, we analyzed an RNA-seq dataset to determine which miRNAs are differentially regulated during hibernation in the dormouse liver. We found that the expression of 19 miRNAs was altered during hibernation; however, only one major miRNA (miR-34a-5p) remained significantly downregulated after correcting for false discovery rate. Gene Ontology, KEGG Pathway Analysis, and DIANA-miRPath predicted that energy metabolism, nuclear-related functions such as histone binding, chromatin- and chromosomal binding, and the cell cycle are processes that may be differentially regulated during hibernation due to miRNA regulation. Taken together, our data suggest that miRNA influence appears to be strongly directed toward suppressing energy-intensive processes in the nucleus hence contributing to extend the animal’s endogenous fuel reserves for the duration of hibernation.},

note = {831},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{declercq_tims2rescore_2025,

title = {TIMS2Rescore: A Data Dependent Acquisition-Parallel Accumulation and Serial Fragmentation-Optimized Data-Driven Rescoring Pipeline Based on MS2Rescore},

author = {Arthur Declercq and Robbe Devreese and Jonas Scheid and Caroline Jachmann and Tim Van Den Bossche and Annica Preikschat and David Gomez-Zepeda and Jeewan Babu Rijal and Aurélie Hirschler and Jonathan R Krieger and Tharan Srikumar and George Rosenberger and Claudia Martelli and Dennis Trede and Christine Carapito and Stefan Tenzer and Juliane S Walz and Sven Degroeve and Robbin Bouwmeester and Lennart Martens and Ralf Gabriels},

url = {https://doi.org/10.1021/acs.jproteome.4c00609},

doi = {10.1021/acs.jproteome.4c00609},

issn = {1535-3893},

year  = {2025},

date = {2025-02-01},

urldate = {2025-02-19},

journal = {Journal of Proteome Research},

abstract = {The high throughput analysis of proteins with mass spectrometry (MS) is highly valuable for understanding human biology, discovering disease biomarkers, identifying therapeutic targets, and exploring pathogen interactions. To achieve these goals, specialized proteomics subfields, including plasma proteomics, immunopeptidomics, and metaproteomics, must tackle specific analytical challenges, such as an increased identification ambiguity compared to routine proteomics experiments. Technical advancements in MS instrumentation can mitigate these issues by acquiring more discerning information at higher sensitivity levels. This is exemplified by the incorporation of ion mobility and parallel accumulation and serial fragmentation (PASEF) technologies in timsTOF instruments. In addition, AI-based bioinformatics solutions can help overcome ambiguity issues by integrating more data into the identification workflow. Here, we introduce TIMS2Rescore, a data-driven rescoring workflow optimized for DDA-PASEF data from timsTOF instruments. This platform includes new timsTOF MS2PIP spectrum prediction models and IM2Deep, a new deep learning-based peptide ion mobility predictor. Furthermore, to fully streamline data throughput, TIMS2Rescore directly accepts Bruker raw mass spectrometry data and search results from ProteoScape and many other search engines, including Sage and PEAKS. We showcase TIMS2Rescore performance on plasma proteomics, immunopeptidomics (HLA class I and II), and metaproteomics data sets. TIMS2Rescore is open-source and freely available at https://github.com/compomics/tims2rescore.},

note = {830},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{benazza_development_2025,

title = {Development of Top-Down Mass Spectrometry Strategies in the Chromatographic Time Scale (LC-TD-MS) for the Extended Characterization of an Anti-EGFR Single-Domain Antibody-Drug Conjugate in Both Reduced and Nonreduced Forms},

author = {Rania Benazza and Léa Letissier and Greg Papadakos and Jen Thom and Helene Diemer and Graham Cotton and Sarah Cianférani and Oscar Hernandez-Alba},

url = {https://doi.org/10.1021/acs.analchem.4c03323},

doi = {10.1021/acs.analchem.4c03323},

issn = {0003-2700},

year  = {2025},

date = {2025-02-01},

urldate = {2025-02-19},

journal = {Analytical Chemistry},

volume = {97},

number = {5},

pages = {2639–2647},

abstract = {Even though mAbs have attracted the biggest interest in the development of therapeutic proteins, next-generation therapeutics such as single-domain antibodies (sdAb) are propelling increasing attention as new alternatives with appealing applications in different clinical areas. These constructs are small therapeutic proteins formed by a variable domain of the heavy chain of an antibody with multiple therapeutic and production benefits compared with their mAb counterparts. These proteins can be subjected to different bioconjugation processes to form single-domain antibody-drug conjugates (sdADCs) and hence increase their therapeutic potency, and akin to other therapeutic proteins, nanobodies and related products require dedicated analytical strategies to fully characterize their primary structure prior to their release to the market. In this study, we report for the first time the extensive sequence characterization of a conjugated anti-EGFR 14 kDa sdADC by using state-of-the-art top-down mass spectrometry strategies in combination with liquid chromatography (LC-TD-MS). Mass analysis revealed a highly homogeneous sample with one conjugated molecule. Subsequently, the reduced sdADC was submitted to different fragmentation techniques, namely, higher-energy collisional dissociation, electron-transfer dissociation, and electron-transfer higher-energy collision dissociation, allowing to unambiguously assess the conjugation site with 24 diagnostic fragment ions and 85% of global sequence coverage. The sequence coverage of the nonreduced protein was significantly lower (around 16%); however, the analysis of the fragmentation spectra corroborated the presence of the intramolecular disulfide bridge along with the localization of the conjugation site. Altogether, our results pinpoint the difficulties and challenges associated with the fragmentation of sdAb-derived formats in the LC time scale due to their remarkable stability as a consequence of the intramolecular disulfide bridge. However, the use of complementary activation techniques along with the identification of specific ion fragments allows an improved sequence coverage, the characterization of the intramolecular disulfide bond, and the unambiguous localization of the conjugation site.},

note = {828},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{mittelheisser_nanomaterials_2025,

title = {Nanomaterials Trigger Functional Anti-Tumoral Responses in Primary Human Immune Cells},

author = {Vincent Mittelheisser and Olivier Lefebvre and Mainak Banerjee and Shayamita Ghosh and Amandine Dupas and Marie-Charlotte Diringer and Juliette Blumberger and Louis Bochler and Sébastien Harlepp and Annabel Larnicol and Angélique Pichot and Tristan Stemmelen and Anne Molitor and Chloé Moritz and Christine Carapito and Raphaël Carapito and Loïc J. Charbonnière and François Lux and Olivier Tillement and Jacky G. Goetz and Alexandre Detappe},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202505729},

doi = {10.1002/advs.202505729},

issn = {2198-3844},

year  = {2025},

date = {2025-01-01},

urldate = {2025-07-18},

journal = {Advanced Science},

volume = {n/a},

number = {n/a},

pages = {e05729},

abstract = {Targeting the immune system with nanoparticles (NPs) to deliver immunomodulatory molecules emerged as a solution to address intra-tumoral immunosuppression and enhance therapeutic response. While the potential of nanoimmunotherapies in reactivating immune cells has been evaluated in several preclinical studies, the impact of drug-free nanomaterials on the immune system remains unknown. Here, the molecular and functional response of human NK cells and pan T cells to a selection of five NPs that are commonly used in biomedical applications are characterized. After a pre-screen to evaluate the toxicity of these nanomaterials on immune cells, ultrasmall silica-based gadolinium (Si-Gd) NPs and poly(lactic-co-glycolic acid) (PLGA) NPs are selected for further investigation. Bulk RNA-sequencing and flow cytometry analysis showcase that PLGA NPs trigger a transcriptional priming toward activation in NK and pan T cells. While PLGA NPs improved NK cells anti-tumoral functions in a cytokines-deprived environment, Si-Gd NPs significantly impaired T cells activation as well as functional responses to a polyclonal antigenic stimulation. Altogether, PLGA NPs are identified as an attractive strategy for reactivating the immune system of cancer patients.},

note = {844},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{otero_synthesis_2025,

title = {Synthesis, Molecular Docking and Biological Evaluation of A-Ring-Carborane-Vitamin D Analogues},

author = {Rocío Otero and Samuel Seoane and Xoán Fernández-Domínguez and Maxime Bourguet and Sarah Cianférani and Carole Peluso-Iltis and Miguel A. Maestro and Román Pérez-Fernández and Natacha Rochel and Antonio Mouriño},

url = {https://www.mdpi.com/1420-3049/30/12/2637},

doi = {10.3390/molecules30122637},

issn = {1420-3049},

year  = {2025},

date = {2025-01-01},

urldate = {2025-07-18},

journal = {Molecules},

volume = {30},

number = {12},

pages = {2637},

abstract = {The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25D3), regulates a number of physiological and pathological processes, including cell proliferation and differentiation. Thousands of analogues of 1,25D3 have been developed with the aim of selective effects for medical use. Here we describe the synthesis of two new unconventional vitamin D analogues bearing A-ring modifications with ortho-carborane (dicarba-o-closo-1,2-dodecaborane) units. The ligands function as agonists for VDR with similar antiproliferative activities as 1,25D3. Whereas mice treated with the analogues 4 and 5 exhibited similar hypercalcemic activities as 1,25D3, only compound 4 and 1,25D3 induced the strong activation of CYP24A1 mRNA expression but not compound 5.},

note = {843},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{schlichter_designing_2025,

title = {Designing New Natural-Mimetic Phosphatidic Acid: a Versatile and Innovative Synthetic Strategy for Glycerophospholipid Research},

author = {Antoine Schlichter and Alexander Wolf and Thomas Ferrand and Aurelien Cocq and Lina Riachy and Steven Vertueux and Brice Beauvais and Marine Courvalet and Paul-Joël Henry and Emeline Tanguy and Louis Gonzales and Rémy Ferlet and Fanny Laguerre and Charles Decraene and Alexia Pellissier and Muriel Sebban and Cyrille Sabot and Lydie Jeandel and Sarah Cianférani and Jean-Marc Strub and Magalie Bénard and Victor Flon and Valérie Peulon-Agasse and Pascal Cardinael and Stéphane Ory and Stéphane Gasman and Pierre-Yves Renard and Maïté Montero-Hadjadje and Nicolas Vitale and Balieu Sébastien},

url = {https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.202510412},

doi = {10.1002/anie.202510412},

issn = {1521-3773},

year  = {2025},

date = {2025-01-01},

urldate = {2025-07-18},

journal = {Angewandte Chemie International Edition},

volume = {n/a},

number = {n/a},

pages = {e202510412},

abstract = {Glycerophospholipids (GPLs) play important roles in cellular compartmentalization and signaling. Among them, phosphatidic acids (PA) exist as many distinct species depending on acyl chain composition, each one potentially displaying unique signaling function. Although the signaling functions of PA have already been demonstrated in multiple cellular processes, the specific roles of individual PA species remain obscure due to a lack of appropriate tools. Indeed, current synthetic PA analogues fail to preserve all the functions of natural PA. To circumvent these limitations, we developed a novel synthetic approach to produce PA analogues without compromising structural integrity of acyl chains. Moreover, addition of a clickable moiety allowed flexible grafting of different molecules to PA analogues for various biological applications. Hence, this innovation also provides powerful tools to investigate specific biological activities of individual PA species, with potential applications in unraveling complex GPL-mediated signaling pathways.},

note = {842},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{kervella_cell_2025,

title = {The cell origin of reactive oxygen species and its implication for evolutionary trade-offs},

author = {Maïly Kervella and Fabrice Bertile and Frédéric Bouillaud and François Criscuolo},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001088/},

doi = {10.1098/rsob.240312},

issn = {2046-2441},

year  = {2025},

date = {2025-01-01},

urldate = {2025-06-18},

journal = {Open Biology},

volume = {15},

number = {4},

pages = {240312},

abstract = {The allocation of resources in animals is shaped by adaptive trade-offs aimed at maximizing fitness. At the heart of these trade-offs, lies metabolism and the conversion of food resources into energy, a process mostly occurring in mitochondria. Yet, the conversion of nutrients to utilizable energy molecules (adenosine triphosphate) inevitably leads to the by-production of reactive oxygen species (ROS) that may cause damage to important biomolecules such as proteins or lipids. The ‘ROS theory of ageing’ has thus proposed that the relationship between lifespan and metabolic rate may be mediated by ROS production. However, the relationship is not as straightforward as it may seem: not only are mitochondrial ROS crucial for various cellular functions, but mitochondria are also actually equipped with antioxidant systems, and many extra-mitochondrial sources also produce ROS. In this review, we discuss how viewing the mitochondrion as a regulator of cellular oxidative homeostasis, not merely a ROS producer, may provide new insights into the role of oxidative stress in the reproduction–survival trade-off. We suggest several avenues to test how mitochondrial oxidative buffering capacity might complement current bioenergetic and evolutionary studies.},

note = {837},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{moreno_borrallo_variation_2025,

title = {Variation in albumin glycation rates in birds suggests resistance to relative hyperglycaemia rather than conformity to the pace of life syndrome hypothesis},

author = {Adrián Moreno Borrallo and Sarahi Jaramillo Ortiz and Christine Schaeffer-Reiss and Benoît Quintard and Benjamin Rey and Pierre Bize and Vincent A Viblanc and Thierry Boulinier and Olivier Chastel and Jorge S Gutiérrez and José A Masero and Fabrice Bertile and Francois Criscuolo},

url = {https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12088674/},

doi = {10.7554/eLife.103205},

issn = {2050-084X},

year  = {2025},

date = {2025-01-01},

urldate = {2025-06-18},

journal = {eLife},

volume = {13},

pages = {RP103205},

abstract = {The pace of life syndrome (POLS) hypothesis suggests that organisms’ life history and physiological and behavioural traits should co-evolve. In this framework, how glycaemia (i.e. blood glucose levels) and its reaction with proteins and other compounds (i.e. glycation) covary with life history traits remain relatively under-investigated, despite the well-documented consequences of glucose and glycation on ageing, and therefore potentially on life history evolution. Birds are particularly relevant in this context given that they have the highest blood glucose levels within vertebrates and still higher mass-adjusted longevity compared to organisms with similar physiology as mammals. We thus performed a comparative analysis on glucose and albumin glycation rates of 88 bird species from 22 orders in relation to life history traits (body mass, clutch mass, maximum lifespan, and developmental time) and diet. Glucose levels correlated positively with albumin glycation rates in a non-linear fashion, suggesting resistance to glycation in species with higher glucose levels. Plasma glucose levels decreased with increasing body mass, but, contrary to what is predicted in the POLS hypothesis, glucose levels increased with maximum lifespan before reaching a plateau. Finally, terrestrial carnivores showed higher albumin glycation compared to omnivores despite not showing higher glucose, which we discuss may be related to additional factors as differential antioxidant levels or dietary composition in terms of fibres or polyunsaturated fatty acids. These results increase our knowledge about the diversity of glycaemia and glycation patterns across birds, pointing towards the existence of glycation resistance mechanisms within comparatively high glycaemic birds., Smaller animals often live shorter lives and use energy at a faster rate than their larger, longer-lived counterparts. This is partly related to differences in their resting metabolic rate, which is the energy expended to maintain basic bodily functions over a given time. For example, mice have high metabolic rates and short lifespans, whereas elephants live much longer and have lower metabolic rates per gram of body mass. However, many birds – despite having high metabolic rates – can live far longer than mammals of a similar size., Birds also have the highest blood glucose levels of any vertebrate group. Through a process known as glycation, glucose and other sugars can attach themselves to molecules such as proteins. The resulting glycated proteins are thought to have negative effects on the body, which can contribute to the ageing process. Therefore, the amount of glycated protein in the blood is often used as a marker for harmful blood glucose levels in humans, which can be indicative of diseases such as diabetes. However, it remained unclear how birds resist the negative impacts of high blood glucose levels and glycation., To investigate, Moreno-Borrallo et al. used measurements from 88 different bird species to explore how glucose levels and glycation of a protein called albumin are related to diet, lifespan and other variables. As expected, species with higher blood glucose levels had higher levels of albumin glycation. However, species with very high glucose levels showed relatively low glycation, suggesting these birds can resist the negative effects of high blood glucose., Surprisingly, the analysis showed that species with higher glucose levels also tended to live longer, although this increase in lifespan eventually levelled off. This is contrary to the idea that species with higher metabolic activity have evolved shorter lifespans. Moreno-Borrallo et al. also showed that glucose levels decrease with body mass but are not related to any other traits. Glycation, on the other hand, is impacted by diet, with land (but not aquatic) carnivores showing higher levels than omnivores., These analyses systematically explore how glucose and glycation levels relate to traits such as lifespan and diet across a wide range of bird species. The results will be valuable to evolutionary biologists and may also have implications for human health, particularly in understanding how glycation can be resisted during ageing. Future research should also focus on identifying which diets may help protect against glycation.},

note = {838},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{le_maho_fieldwork_2025,

title = {Fieldwork on animals living in extreme conditions as a source of biomedical innovation},

author = {Yvon Le Maho and Aurélie Tasiemski and Fabrice Bertile and Philippe Bulet},

url = {https://linkinghub.elsevier.com/retrieve/pii/S2949704324000350},

doi = {10.1016/j.soh.2024.100096},

issn = {29497043},

year  = {2025},

date = {2025-01-01},

urldate = {2025-02-19},

journal = {Science in One Health},

volume = {4},

pages = {100096},

abstract = {Most biomedical research on animals is based on the handful of the so-called standard model organisms, i.e. laboratory mice, rats or Drosophila, but the keys to some important biomedical questions may simply not be found in these. However, compared with the high number of molecules originating from plants in clinical use, and with the countless unique adaption mechanisms that animals have developed over the course of evolution to cope with environmental constrains, there is still few investigations on wild animals with biomedical objectives, and field studies are far fewer. A major limitation is insufficient funding, the main causes of which we analyze. We argue, however, that fieldwork is a key driver in generating new scientific knowledge as part of a One Health approach, by observing/documenting and understanding the diverse and largely unexplored biological processes evolved by animals adapted to unusual environmental conditions, which would be extreme conditions for humans. These conditions do not only refer to extreme temperatures, since lack of food or water, high pressures or lack of oxygen, are clearly extreme constraints. To conduct this research, there are serious limitations we propose to address. Specific techniques and methods are requested, not only to work in extreme environments, but also to minimize the ecological footprint of field work. The erosion of biodiversity is a major threat. The reduction of animal disturbance, a key issue, requires specific technologies and expertise. An ethical approach is requested, for the sake of transparency and to comply with the Nagoya Protocol on genetic resources. An interdisciplinary expertise and a meticulous planning are requested to overcome the field constraints and interface the associated laboratory work. We recommend focusing on the major threats to global human health today, which wild animals appear to resist particularly well, such as antibioresistance and diseases associated with lifestyle and senescence.},

note = {833},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{gervason_isc_2025,

title = {The ISC machinery assembles [2Fe–2S] clusters by formation and fusion of [1Fe–1S] precursors},

author = {Sylvain Gervason and Rafal Dutkiewicz and Kristian Want and Rania Benazza and Rémi Mor-Gautier and Aneta Grabinska-Rogala and Christina Sizun and Oscar Hernandez-Alba and Sarah Cianferani and Bruno Guigliarelli and Bénédicte Burlat and Benoit D’Autréaux},

url = {https://www.nature.com/articles/s41589-024-01818-8},

doi = {10.1038/s41589-024-01818-8},

issn = {1552-4469},

year  = {2025},

date = {2025-01-01},

urldate = {2025-02-19},

journal = {Nature Chemical Biology},

pages = {1–12},

abstract = {Iron–sulfur clusters are essential metallocofactors synthesized by multiprotein machineries via an unclear multistep process. Here we report a step-by-step dissection of the [2Fe–2S] cluster assembly process by the Escherichia coli iron–sulfur cluster (ISC) assembly machinery using an in vitro reconstituted system and a combination of biochemical and spectroscopic techniques. We show that this process is initiated by iron binding to the scaffold protein IscU, which triggers persulfide insertion by the cysteine desulfurase IscS upon the formation of a complex with IscU. Then, the persulfide is cleaved into sulfide by the ferredoxin Fdx, leading to a [1Fe–1S] precursor. IscU dissociates from IscS, dimerizes and generates a bridging [2Fe–2S] cluster by fusion of two [1Fe–1S] precursors. The IscU dimer ultimately dissociates into a monomer, ready to transfer its [2Fe–2S] cluster to acceptors. These data provide a comprehensive description of the [2Fe–2S] cluster assembly process by the ISC assembly machinery, highlighting the formation of key intermediates through a tightly concerted process.},

note = {835},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cantero_detection_2025,

title = {Detection of textitBorrelia burgdorferi sensu lato by proteomics: a complementary diagnosis tool on erythema migrans biopsies},

author = {Paola Cantero and Laurence Ehret-Sabatier and Cédric Lenormand and Yves Hansmann and Erik Sauleau and Laurence Zilliox and Benoit Westermann and Benoit Jaulhac and Didier Mutter and Cathy Barthel and Pauline Perdu-Alloy and Martin Martinot and Dan Lipsker and Nathalie Boulanger},

url = {https://www.sciencedirect.com/science/article/pii/S1198743X24004968},

doi = {10.1016/j.cmi.2024.10.014},

issn = {1198-743X},

year  = {2025},

date = {2025-01-01},

urldate = {2025-01-07},

journal = {Clinical Microbiology and Infection},

volume = {31},

number = {1},

pages = {78–86},

abstract = {Objectives 

We have developed targeted proteomics in the context of Lyme borreliosis (LM) as a new direct diagnostic tool for detecting Borrelia proteins in the skin of patients with erythema migrans. If satisfactory, this proteomic technique could be used in addition to culture and/or PCR for disseminated infections where Borrelia detection is essential to demonstrate active infection. In these infections, the diagnosis is indirect and relies mainly on serology. 

Methods 

We recruited 46 patients with LM and 11 controls and collected two skin biopsies from each patient. One biopsy was used for Borrelia burgdorferi sensu lato PCR and culture and the other one was for targeted mass-spectrometry-based proteomics. Six markers of infection were selected for proteomics: Outer surface protein C (OspC), flagellin, enolase, lipoprotein gitextbar365823350, decorin binding protein A, and glyceraldehyde-3-phosphate dehydrogenase. 

Results 

Culturing Borrelia from the biopsies increased the sensitivity of the methods. Among the patients included for analysis, 61% (28 patients), 61% (28), and 46% (21) were detected as positive by proteomics, PCR, and culture, respectively. PCR and proteomics were complementary. OspC and flagellin were the most frequently detected protein markers of infection by proteomics, which in some patients, detected up to nine peptides for the flagellin. 

Discussion 

It is possible to identify bacterial makers from the skin by proteomics. Our approach can be used to diagnose tick-borne diseases such as LM. 

Trial registration 

clinicaltrials.gov identifier: NCT02414789.},

note = {834},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{de_napoli_reduced_2025,

title = {Reduced ATP turnover during hibernation in relaxed skeletal muscle},

author = {Cosimo De Napoli and Luisa Schmidt and Mauro Montesel and Laura Cussonneau and Samuele Sanniti and Lorenzo Marcucci and Elena Germinario and Jonas Kindberg and Alina Lynn Evans and Guillemette Gauquelin-Koch and Marco Narici and Fabrice Bertile and Etienne Lefai and Marcus Krüger and Leonardo Nogara and Bert Blaauw},

url = {https://www.nature.com/articles/s41467-024-55565-4},

doi = {10.1038/s41467-024-55565-4},

issn = {2041-1723},

year  = {2025},

date = {2025-01-01},

urldate = {2025-01-06},

journal = {Nature Communications},

volume = {16},

number = {1},

pages = {80},

abstract = {Hibernating brown bears, due to a drastic reduction in metabolic rate, show only moderate muscle wasting. Here, we evaluate if ATPase activity of resting skeletal muscle myosin can contribute to this energy sparing. By analyzing single muscle fibers taken from the same bears, either during hibernation or in summer, we find that fibers from hibernating bears have a mild decline in force production and a significant reduction in ATPase activity. Single fiber proteomics, western blotting, and immunohistochemical analyses reveal major remodeling of the mitochondrial proteome during hibernation. Furthermore, using bioinformatical approaches and western blotting we find that phosphorylated myosin light chain, a known stimulator of basal myosin ATPase activity, is decreased in hibernating and disused muscles. These results suggest that skeletal muscle limits energy loss by reducing myosin ATPase activity, indicating a possible role for myosin ATPase activity modulation in multiple muscle wasting conditions.},

note = {832},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{aubry_accelerated_2025,

title = {Accelerated aging modulates the toxicological properties of the diazo tattoo pigment PO13},

author = {Lise Aubry and Marianne Vitipon and Aurélie Hirschler and Hélène Diemer and Thierry Rabilloud and Christine Carapito and Thierry Douki},

url = {https://www.nature.com/articles/s41598-024-83713-9},

doi = {10.1038/s41598-024-83713-9},

issn = {2045-2322},

year  = {2025},

date = {2025-01-01},

urldate = {2025-01-06},

journal = {Scientific Reports},

volume = {15},

number = {1},

pages = {695},

abstract = {Pigment particles used in tattooing may exert long terms effect by releasing diffusible degradation products. In the present work, aqueous suspensions of the organic orange diazo pigment PO13 were aged by exposure to simulated sunlight at 40 °C. The morphology and the surface charge of PO13 particles were barely modified upon aging, but primary particles were released by de-agglomeration. Soluble photoproducts were detected in the liquid fractions. One of this photoproduct (DCBP) was produced in large amount in suspension in isopropanol and purified. The toxicological profiles of aged suspensions, their soluble fractions and DCBP were then determined on the keratinocyte cell line HaCaT. Impact of suspensions of PO13 on viability was hardly affected by aging. In contrast, the soluble fractions were more toxic after photo-aging. Suspensions and filtrates induced neither release of reactive oxygen species nor formation of DNA strand breaks. The samples exhibited only limited effects on the proteome of HaCaT cells. Conversely, DCBP was cytotoxic and induced the production of ROS, but was not genotoxic. DCBP was found to activate CYP450 monooxygenases known to be involved in the metabolism of xenobiotics. Altogether, our results show that aging of PO13 leads to the release of toxic soluble compounds.},

note = {827},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{boos_antibody-vincristine_2024,

title = {Antibody-Vincristine Conjugates as Potent Anticancer Therapeutic Agents},

author = {Agathe Boos and Julien Most and Héloïse Cahuzac and Louis Moreira da Silva and François Daubeuf and Stéphane Erb and Sarah Cianférani and Oscar Hernandez-Alba and Constantin Semenchenko and Igor Dovgan and Sergii Kolodych and Alexandre Detappe and Françoise Dantzer and Alain Wagner and Maria Zeniou and Guilhem Chaubet},

url = {https://doi.org/10.1021/acs.jmedchem.4c02425},

doi = {10.1021/acs.jmedchem.4c02425},

issn = {0022-2623},

year  = {2024},

date = {2024-12-01},

urldate = {2025-01-06},

journal = {Journal of Medicinal Chemistry},

abstract = {Antibody-drug conjugates (ADCs) are a well-established class of therapeutics primarily used in oncology to selectively deliver highly cytotoxic agents into cancer cells. While ADCs should theoretically spare healthy tissues and diminish side effects in patients, off-target toxicity is still observed, all the more serious, as the drugs are extremely potent. In the quest toward safer payloads, we used the conventional chemotherapeutic drug vincristine to develop antibody-vincristine conjugates. Vincristine was N-alkylated with a cleavable linker and the resulting linker-payload conjugated to free cysteines of antibodies. We show that trastuzumab-vincristine conjugates display subnanomolar potency in vitro on HER2-positive cells, 2 orders of magnitude lower than free vincristine and comparable with marketed ADC. In vivo, trastuzumab-vincristine conjugates led to remarkable efficacy when compared to two standards of care, with complete tumor regression just 9 days after single administration. This highlights the untapped potential of the chemotherapeutic arsenal toward the development of novel ADC.},

note = {817},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{robin_when_2024,

title = {When the King penguin meets macroplastics: A first case reported in the Crozet archipelago, Southern Indian Ocean},

author = {Jean-Patrice Robin and Gaël Bardon and Fabrice Bertile and Pierre Carette and Anne Cillard and Lana Lenourry and Céline Le Bohec},

url = {https://www.sciencedirect.com/science/article/pii/S0025326X24010701},

doi = {10.1016/j.marpolbul.2024.117093},

issn = {0025-326X},

year  = {2024},

date = {2024-12-01},

urldate = {2024-12-13},

journal = {Marine Pollution Bulletin},

volume = {209},

pages = {117093},

abstract = {Plastics are one of the major forms of anthropogenic pollution. This waste can affect the individual survival in many species, including seabirds. The Southern Ocean ecosystems are thought to be less affected by this pollution, due to the low human presence and the natural protective barrier provided by southern oceanic fronts. Here, we report the first observation of macroplastic ingestion in two dead King penguins (Aptenodytes patagonicus) in the Crozet archipelago located south of these fronts. There is no evidence that the macroplastic fragments found in their stomach were the direct cause of death. We suggest that they were ingested by being confused with stones they used for food grinding. Although it is difficult to assess the local or distant origin of these macroplastics, efforts to collect waste from sites as remote as the subantarctic islands must become standard practice to ensure that such ingestions do not become commonplace.},

note = {824},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{reinert_therapeutic_2024,

title = {Therapeutic Monoclonal Antibody─Antidrug Antibody Affinity Constant Determination Using Capillary Electrophoresis–Tandem Mass Spectrometry},

author = {Tessa Reinert and Pascal Houzé and Nathalie Mignet and Aynur Naghizade and Lola Alez-Martin and Oscar Hernandez-Alba and Armand Leclerc and Sarah Cianferani and Rabah Gahoual and Yannis-Nicolas Francois},

url = {https://doi.org/10.1021/acs.analchem.4c02932},

doi = {10.1021/acs.analchem.4c02932},

issn = {0003-2700},

year  = {2024},

date = {2024-12-01},

urldate = {2024-12-13},

journal = {Analytical Chemistry},

volume = {96},

number = {49},

pages = {19286–19293},

abstract = {Monoclonal antibody (mAbs) therapeutics cannot evade the occurrence of adverse effects. Thus, mAbs are commonly triggering immune responses corresponding to the expression of antidrug antibodies. Antidrug antibodies can neutralize mAbs, leading to their inhibition and hasten clearance, which dramatically hampers their therapeutic effects. Therefore, studies concerning the affinity between a mAbs and the corresponding antidrug antibody are demonstrating a growing interest to further understand the outcome of biotherapeutics after administration. We describe a novel analytical approach for the determination of the dissociation constant (Kd) between a mAb and an antidrug antibody using capillary electrophoresis coupled to mass spectrometry (CE-MS/MS). The CE-MS/MS method employs a competitive assay, followed by the quantification of the residual amount of the active mAbs. The methodology allowed for the measurement of Kd using serum samples without the implementation of immobilization to achieve protein–protein interaction. This characteristic enabled us to generate the interaction in conditions reflecting the physiological environment. A mathematical treatment was developed to calculate Kd from MS/MS data, taking into account the stoichiometry of the mAbs/antidrug antibody complex and the bivalent properties of the two immunoglobulins. Prior to CE-MS/MS analysis, the interaction of the two proteins was studied by using mass photometry (MP) to determine equilibrium conditions and complexation stoichiometry. CE-MS/MS was used to investigate the interaction between infliximab and a neutralizing anti-infliximab antibody. Results allowed to measure a Kd of 14.4 ± 2.9 nM. MS instrumentation sensitivity and specificity showed to be relevant to achieve accurate and robust Kd measurements for strong interactions in the nanomolar range.},

note = {823},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{abeza_hsp90r2tp_2024,

title = {The HSP90/R2TP Quaternary Chaperone Scaffolds Assembly of the TSC Complex},

author = {Claire Abéza and Philipp Busse and Ana C. F. Paiva and Marie-Eve Chagot and Justine Schneider and Marie-Cécile Robert and Franck Vandermoere and Christine Schaeffer and Bruno Charpentier and Pedro M. F. Sousa and Tiago M. Bandeiras and Xavier Manival and Sarah Cianferani and Edouard Bertrand and Céline Verheggen},

url = {https://linkinghub.elsevier.com/retrieve/pii/S0022283624004698},

doi = {10.1016/j.jmb.2024.168840},

issn = {00222836},

year  = {2024},

date = {2024-12-01},

urldate = {2024-12-13},

journal = {Journal of Molecular Biology},

volume = {436},

number = {23},

pages = {168840},

abstract = {The R2TP chaperone is composed of the RUVBL1/RUVBL2 AAA+ ATPases and two adapter proteins, RPAP3 and PIH1D1. Together with HSP90, it functions in the assembly of macromolecular complexes that are often involved in cell proliferation. Here, proteomic experiments using the isolated PIH domain reveals additional R2TP partners, including the Tuberous Sclerosis Complex (TSC) and many transcriptional complexes. The TSC is a key regulator of mTORC1 and is composed of TSC1, TSC2 and TBC1D7. We show a direct interaction of TSC1 with the PIH phospho-binding domain of PIH1D1, which is, surprisingly, phosphorylation independent. Via the use of mutants and KO cell lines, we observe that TSC2 makes independent interactions with HSP90 and the TPR domains of RPAP3. Moreover, inactivation of PIH1D1 or the RUVBL1/2 ATPase activity inhibits the association of TSC1 with TSC2. Taken together, these data suggest a model in which the R2TP recruits TSC1 via PIH1D1 and TSC2 via RPAP3 and HSP90, and use the chaperone-like activities of RUVBL1/2 to stimulate their assembly.},

note = {814},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{demeulemeester_msqrob2ptm_2024,

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

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

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

issn = {1535-9484 (ELECTRONIC) 1535-9476 (LINKING)},

year  = {2024},

date = {2024-12-01},

journal = {Mol Cell Proteomics},

pages = {100708},

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

note = {788},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{grea_subcutaneous_2024,

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

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

doi = {10.1002/adma.202308738},

issn = {0935-9648},

year  = {2024},

date = {2024-12-01},

journal = {Advanced Materials},

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

note = {785},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{beauvieux_tracing_2024,

title = {Tracing troubles: Unveiling the hidden impact of inorganic contamination on juvenile green sea turtle},

author = {Anaïs Beauvieux and Jérôme Bourjea and Jean-Marc Fromentin and Claire Jean and Stéphane Ciccione and Katia Ballorain and Diego Romero and Zahraa Dbouk and Aurélie Hirschler and Fabrice Bertile and Quentin Schull},

url = {https://linkinghub.elsevier.com/retrieve/pii/S0025326X24010257},

doi = {10.1016/j.marpolbul.2024.117048},

issn = {0025326X},

year  = {2024},

date = {2024-11-01},

urldate = {2024-12-13},

journal = {Marine Pollution Bulletin},

volume = {208},

pages = {117048},

abstract = {Human activities and climate change have negatively affected the world’s oceans, leading to a decline of 30 to 60 % in coastal ecosystems’ biodiversity and habitats. The projected increase in the human population to 9.7 billion by 2050 raises concerns about the sustainability of marine ecosystem conservation and exploitation. Marine turtles, as sentinel species, accumulate contaminants, including trace elements, due to their extensive migration and long-life span. However, there is a lack of data on the degree of contamination and their effects on marine turtles’ health. This study focuses on assessing in-situ inorganic contamination in juvenile green sea turtles from La R´eunion Island and its short-term impact on individual health, using conventional biomarkers and proteomics. The goals include examining contamination patterns in different tissues and identifying potential new biomarkers for long-term monitoring and conservation efforts. The study identified differential metal contamination between blood and scute samples, which could help illuminate temporal exposure to trace elements in turtle individuals. We also found that some conventional biomarkers were related to trace element exposure, while the proteome responded differently to various contaminant mixtures. Immune processes, cellular organization, and metabolism were impacted, indicating that contaminant mixtures in the wild would have an effect on turtle’s health. Fifteen biomarker candidates associated with strong molecular responses of sea turtle to trace element contamination are proposed for future long-term monitoring. The findings emphasize the importance of using proteomic approaches to detect subtle physiological responses to contaminants in the wild and support the need for non-targeted analysis of trace elements in the biomonitoring of sea turtle health.},

note = {815},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{busselez_remodelling_2024,

title = {Remodelling of Rea1 linker domain drives the removal of assembly factors from pre-ribosomal particles},

author = {Johan Busselez and Geraldine Koenig and Carine Dominique and Torben Klos and Deepika Velayudhan and Piotr Sosnowski and Nils Marechal and Corinne Crucifix and Hugo Gizardin-Fredon and Sarah Cianferani and Benjamin Albert and Yves Henry and Anthony K. Henras and Helgo Schmidt},

url = {https://www.nature.com/articles/s41467-024-54698-w},

doi = {10.1038/s41467-024-54698-w},

issn = {2041-1723},

year  = {2024},

date = {2024-11-01},

urldate = {2024-12-13},

journal = {Nature Communications},

volume = {15},

number = {1},

pages = {10309},

abstract = {The ribosome maturation factor Rea1 (or Midasin) catalyses the removal of assembly factors from large ribosomal subunit precursors and promotes their export from the nucleus to the cytosol. Rea1 consists of nearly 5000 amino-acid residues and belongs to the AAA+ protein family. It consists of a ring of six AAA+ domains from which the ≈1700 amino-acid residue linker emerges that is subdivided into stem, middle and top domains. A flexible and unstructured D/E rich region connects the linker top to a MIDAS (metal ion dependent adhesion site) domain, which is able to bind the assembly factor substrates. Despite its key importance for ribosome maturation, the mechanism driving assembly factor removal by Rea1 is still poorly understood. Here we demonstrate that the Rea1 linker is essential for assembly factor removal. It rotates and swings towards the AAA+ ring following a complex remodelling scheme involving nucleotide independent as well as nucleotide dependent steps. ATP-hydrolysis is required to engage the linker with the AAA+ ring and ultimately with the AAA+ ring docked MIDAS domain. The interaction between the linker top and the MIDAS domain allows direct force transmission for assembly factor removal.},

note = {818},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{beaumal_improved_2024,

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

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

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

issn = {1618-2642},

year  = {2024},

date = {2024-11-01},

journal = {Analytical and Bioanalytical Chemistry},

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

note = {787},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{djebar_astrogliosis_2024,

title = {Astrogliosis and neuroinflammation underlie scoliosis upon cilia dysfunction},

author = {M. Djebar and I. Anselme and G. Pezeron and P. L. Bardet and Y. Cantaut-Belarif and A. Eschstruth and D. Lopez-Santos and H. Le Ribeuz and A. Jenett and H. Khoury and J. Veziers and C. Parmentier and A. Hirschler and C. Carapito and R. Bachmann-Gagescu and S. Schneider-Maunoury and C. Vesque},

doi = {10.7554/eLife.96831},

issn = {2050-084X (ELECTRONIC) 2050-084X (LINKING)},

year  = {2024},

date = {2024-10-01},

journal = {Elife},

volume = {13},

abstract = {Cilia defects lead to scoliosis in zebrafish, but the underlying pathogenic mechanisms are poorly understood and may diverge depending on the mutated gene. Here, we dissected the mechanisms of scoliosis onset in a zebrafish mutant for the rpgrip1l gene encoding a ciliary transition zone protein. rpgrip1l mutant fish developed scoliosis with near-total penetrance but asynchronous onset in juveniles. Taking advantage of this asynchrony, we found that curvature onset was preceded by ventricle dilations and was concomitant to the perturbation of Reissner fiber polymerization and to the loss of multiciliated tufts around the subcommissural organ. Rescue experiments showed that Rpgrip1l was exclusively required in foxj1a-expressing cells to prevent axis curvature. Genetic interactions investigations ruled out Urp1/2 levels as a main driver of scoliosis in rpgrip1 mutants. Transcriptomic and proteomic studies identified neuroinflammation associated with increased Annexin levels as a potential mechanism of scoliosis development in rpgrip1l juveniles. Investigating the cell types associated with annexin2 over-expression, we uncovered astrogliosis, arising in glial cells surrounding the diencephalic and rhombencephalic ventricles just before scoliosis onset and increasing with time in severity. Anti-inflammatory drug treatment reduced scoliosis penetrance and severity and this correlated with reduced astrogliosis and macrophage/microglia enrichment around the diencephalic ventricle. Mutation of the cep290 gene encoding another transition zone protein also associated astrogliosis with scoliosis. Thus, we propose astrogliosis induced by perturbed ventricular homeostasis and associated with immune cell activation as a novel pathogenic mechanism of zebrafish scoliosis caused by cilia dysfunction.},

note = {820},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{molitor_pleiotropic_2024,

title = {A pleiotropic recurrent dominant ITPR3 variant causes a complex multisystemic disease},

author = {A. Molitor and A. Lederle and M. Radosavljevic and V. Sapuru and M. E. Zavorka Thomas and J. Yang and M. Shirin and V. Collin-Bund and K. Jerabkova-Roda and Z. Miao and A. Bernard and V. Rolli and P. Grenot and C. N. Castro and M. Rosenzwajg and E. G. Lewis and R. Person and U. S. Esperon-Moldes and M. Kaare and P. T. Nokelainen and N. A. Batzir and G. Z. Hoffer and N. Paul and T. Stemmelen and L. Naegely and A. Hanauer and S. Bibi-Triki and S. Grun and S. Jung and I. Busnelli and K. Tripolszki and R. Al-Ali and N. Ordonez and P. Bauer and E. Song and K. Zajo and S. Partida-Sanchez and F. Robledo-Avila and A. Kumanovics and Y. Louzoun and A. Hirschler and A. Pichot and O. Toker and C. A. M. Mejia and N. Parvaneh and E. Knapp and J. H. Hersh and H. Kenney and O. M. Delmonte and L. D. Notarangelo and J. G. Goetz and S. B. Kahwash and C. Carapito and R. P. S. Bajwa and C. Thomas and S. Ehl and B. Isidor and R. Carapito and R. S. Abraham and R. K. Hite and N. Marcus and A. Bertoli-Avella and S. Bahram},

doi = {10.1126/sciadv.ado5545},

issn = {2375-2548 (ELECTRONIC) 2375-2548 (LINKING)},

year  = {2024},

date = {2024-09-01},

journal = {Sci Adv},

volume = {10},

number = {37},

pages = {eado5545},

abstract = {Inositol 1,4,5-trisphosphate (IP3) receptor type 1 (ITPR1), 2 (ITPR2), and 3 (ITPR3) encode the IP3 receptor (IP3R), a key player in intracellular calcium release. In four unrelated patients, we report that an identical ITPR3 de novo variant-NM_002224.3:c.7570C>T, p.Arg2524Cys-causes, through a dominant-negative effect, a complex multisystemic disorder with immunodeficiency. This leads to defective calcium homeostasis, mitochondrial malfunction, CD4(+) lymphopenia, a quasi-absence of naive CD4(+) and CD8(+) cells, an increase in memory cells, and a distinct TCR repertoire. The calcium defect was recapitulated in Jurkat knock-in. Site-directed mutagenesis displayed the exquisite sensitivity of Arg(2524) to any amino acid change. Despite the fact that all patients had severe immunodeficiency, they also displayed variable multisystemic involvements, including ectodermal dysplasia, Charcot-Marie-Tooth disease, short stature, and bone marrow failure. In conclusion, unlike previously reported ITPR1-3 deficiencies leading to narrow, mainly neurological phenotypes, a recurrent dominant ITPR3 variant leads to a multisystemic disease, defining a unique role for IP3R3 in the tetrameric IP3R complex.},

note = {822},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rady_protocol_2024,

title = {Protocol to generate, purify, and analyze antibody-oligonucleotide conjugates from off-the-shelf antibodies},

author = {T. Rady and V. Lehot and J. Most and S. Erb and S. Cianferani and G. Chaubet and N. Basse and A. Wagner},

doi = {10.1016/j.xpro.2024.103329},

issn = {2666-1667 (ELECTRONIC) 2666-1667 (LINKING)},

year  = {2024},

date = {2024-09-01},

journal = {STAR Protoc},

volume = {5},

number = {4},

pages = {103329},

abstract = {Antibody-oligonucleotide conjugates (AOCs) are a fast-expanding modality for targeted delivery of therapeutic oligonucleotides to tissues. Here, we present a protocol to generate, purify, and analyze AOCs from off-the-shelf antibodies. We describe steps to conjugate single/double-stranded oligonucleotides bearing amine handles to linkers and, then, to antibodies using well-established chemistry. In addition, we provide details regarding the purification techniques and analytical methods suitable for AOC. This protocol can be applied for several purposes where AOC is a modality of interest. For complete details on the use and execution of this protocol, please refer to Rady et al.(1).},

note = {812},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{ripoll_supramolecular_2024,

title = {Supramolecular Bioconjugation Strategy for Antibody-Targeted Delivery of siRNA},

author = {M. Ripoll and H. Cahuzac and I. Dovgan and S. Ursuegui and P. Neuberg and S. Erb and S. Cianferani and A. Kichler and J. S. Remy and A. Wagner},

doi = {10.1021/acs.bioconjchem.4c00304},

issn = {1520-4812 (ELECTRONIC) 1043-1802 (LINKING)},

year  = {2024},

date = {2024-09-01},

journal = {Bioconjug Chem},

abstract = {RNA interference is a widely used biological process by which double-stranded RNA induces sequence-specific gene silencing by targeting mRNA for degradation. However, the physicochemical properties of siRNAs make their delivery extremely challenging, thus limiting their bioavailability at the target site. In this context, we developed a versatile and selective siRNA delivery system of a trastuzumab-conjugated nanocarrier. These immunoconjugates consist of the assembly by electrostatic interactions of an oligonucleotide-modified antibody with a cationic micelle for the targeted delivery of siRNA in HER2-overexpressing cancer cells. Results show that, when associated with the corresponding siRNA at the appropriate N/P ratio, our supramolecular assembly was able to efficiently induce luciferase and PLK-1 gene silencing in a cell-selective manner in vitro.},

note = {813},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{iacobucci_proteomic_2024,

title = {Proteomic Profiling of Antimalarial Plasmodione Using 3-Benz(o)ylmenadione Affinity-Based Probes},

author = {I. Iacobucci and V. Monaco and A. Hovasse and B. Dupouy and R. Keumoe and B. Cichocki and M. Elhabiri and B. Meunier and J. M. Strub and M. Monti and S. Cianferani and S. A. Blandin and C. Schaeffer-Reiss and E. Davioud-Charvet},

doi = {10.1002/cbic.202400187},

issn = {1439-7633 (ELECTRONIC) 1439-4227 (LINKING)},

year  = {2024},

date = {2024-08-01},

journal = {ChemBioChem},

volume = {25},

number = {15},

pages = {e202400187},

abstract = {Understanding the mechanisms of drug action in malarial parasites is crucial for the development of new drugs to combat infection and to counteract drug resistance. Proteomics is a widely used approach to study host-pathogen systems and to identify drug protein targets. Plasmodione is an antiplasmodial early-lead drug exerting potent activities against young asexual and sexual blood stages in vitro with low toxicity to host cells. To elucidate its molecular mechanisms, an affinity-based protein profiling (AfBPP) approach was applied to yeast and P. falciparum proteomes. New (pro-) AfBPP probes based on the 3-benz(o)yl-6-fluoro-menadione scaffold were synthesized. With optimized conditions of both photoaffinity labeling and click reaction steps, the AfBPP protocol was then applied to a yeast proteome, yielding 11 putative drug-protein targets. Among these, we found four proteins associated with oxidoreductase activities, the hypothesized type of targets for plasmodione and its metabolites, and other proteins associated with the mitochondria. In Plasmodium parasites, the MS analysis revealed 44 potential plasmodione targets that need to be validated in further studies. Finally, the localization of a 3-benzyl-6-fluoromenadione AfBPP probe was studied in the subcellular structures of the parasite at the trophozoite stage.},

note = {809},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{munoz-diaz_proteomic_2024,

title = {Proteomic profiling of Arabidopsis nuclei reveals distinct protein accumulation kinetics upon heat stress},

author = {E. Munoz-Diaz and I. Fuenzalida-Valdivia and T. Darriere and A. Bures and F. Blanco-Herrera and M. Rompais and C. Carapito and J. Saez-Vasquez},

doi = {10.1038/s41598-024-65558-4},

issn = {2045-2322 (ELECTRONIC) 2045-2322 (LINKING)},

year  = {2024},

date = {2024-08-01},

journal = {Sci Rep},

volume = {14},

number = {1},

pages = {18914},

abstract = {Heat stress (HS) impacts the nuclear proteome and, subsequently, protein activities in different nuclear compartments. In Arabidopsis thaliana, a short exposure to 37 degrees C leads to loss of the standard tripartite architecture of the nucleolus, the most prominent nuclear substructure, and, consequently, affects the assembly of ribosomes. Here, we report a quantitative label-free LC‒MS/MS (Liquid Chromatography coupled to tandem Mass Spectrometry) analysis to determine the nuclear proteome of Arabidopsis at 22 degrees C, HS (37 degrees C for 4 and 24 h), and a recovery phase. This analysis identified ten distinct groups of proteins based on relative abundance changes in the nucleus before, during and after HS: Early, Late, Transient, Early Persistent, Late Persistent, Recovery, Early-Like, Late-Like, Transient-Like and Continuous Groups (EG, LG, TG, EPG, LPG, RG, ELG, LLG, TLG and CG, respectively). Interestingly, the RNA polymerase I subunit NRPA3 and other main nucleolar proteins, including NUCLEOLIN 1 and FIBRILLARIN 1 and 2, were detected in RG and CG, suggesting that plants require increased nucleolar activity and likely ribosome assembly to restore protein synthesis after HS.},

note = {807},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{caldi_gomes_multiomic_2024,

title = {Multiomic ALS signatures highlight subclusters and sex differences suggesting the MAPK pathway as therapeutic target},

author = {L. Caldi Gomes and S. Hanzelmann and F. Hausmann and R. Khatri and S. Oller and M. Parvaz and L. Tzeplaeff and L. Pasetto and M. Gebelin and M. Ebbing and C. Holzapfel and S. F. Columbro and S. Scozzari and J. Knoferle and I. Cordts and A. F. Demleitner and M. Deschauer and C. Dufke and M. Sturm and Q. Zhou and P. Zelina and E. Sudria-Lopez and T. B. Haack and S. Streb and M. Kuzma-Kozakiewicz and D. Edbauer and R. J. Pasterkamp and E. Laczko and H. Rehrauer and R. Schlapbach and C. Carapito and V. Bonetto and S. Bonn and P. Lingor},

doi = {10.1038/s41467-024-49196-y},

issn = {2041-1723 (ELECTRONIC) 2041-1723 (LINKING)},

year  = {2024},

date = {2024-06-01},

journal = {Nat Commun},

volume = {15},

number = {1},

pages = {4893},

abstract = {Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease and lacks effective disease-modifying treatments. This study utilizes a comprehensive multiomic approach to investigate the early and sex-specific molecular mechanisms underlying ALS. By analyzing the prefrontal cortex of 51 patients with sporadic ALS and 50 control subjects, alongside four transgenic mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS), we have uncovered significant molecular alterations associated with the disease. Here, we show that males exhibit more pronounced changes in molecular pathways compared to females. Our integrated analysis of transcriptomes, (phospho)proteomes, and miRNAomes also identified distinct ALS subclusters in humans, characterized by variations in immune response, extracellular matrix composition, mitochondrial function, and RNA processing. The molecular signatures of human subclusters were reflected in specific mouse models. Our study highlighted the mitogen-activated protein kinase (MAPK) pathway as an early disease mechanism. We further demonstrate that trametinib, a MAPK inhibitor, has potential therapeutic benefits in vitro and in vivo, particularly in females, suggesting a direction for developing targeted ALS treatments.},

note = {811},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{mons_regulations_2024,

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

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

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

issn = {1873-3344 (ELECTRONIC) 0162-0134 (LINKING)},

year  = {2024},

date = {2024-06-01},

journal = {J Inorg Biochem},

volume = {255},

pages = {112535},

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

note = {798},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{very_o-glcnacylation_2024,

title = {O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts},

author = {N. Very and C. Boulet and C. Gheeraert and A. Berthier and M. Johanns and M. Bou Saleh and L. Guille and F. Bray and J. M. Strub and M. Bobowski-Gerard and F. P. Zummo and E. Vallez and O. Molendi-Coste and E. Woitrain and S. Cianferani and D. Montaigne and L. C. Ntandja-Wandji and L. Dubuquoy and J. Dubois-Chevalier and B. Staels and P. Lefebvre and J. Eeckhoute},

doi = {10.1038/s41419-024-06773-9},

issn = {2041-4889 (ELECTRONIC)},

year  = {2024},

date = {2024-06-01},

journal = {Cell Death Dis},

volume = {15},

number = {6},

pages = {391},

abstract = {Tissue injury causes activation of mesenchymal lineage cells into wound-repairing myofibroblasts (MFs), whose uncontrolled activity ultimately leads to fibrosis. Although this process is triggered by deep metabolic and transcriptional reprogramming, functional links between these two key events are not yet understood. Here, we report that the metabolic sensor post-translational modification O-linked beta-D-N-acetylglucosaminylation (O-GlcNAcylation) is increased and required for myofibroblastic activation. Inhibition of protein O-GlcNAcylation impairs archetypal myofibloblast cellular activities including extracellular matrix gene expression and collagen secretion/deposition as defined in vitro and using ex vivo and in vivo murine liver injury models. Mechanistically, a multi-omics approach combining proteomic, epigenomic, and transcriptomic data mining revealed that O-GlcNAcylation controls the MF transcriptional program by targeting the transcription factors Basonuclin 2 (BNC2) and TEA domain transcription factor 4 (TEAD4) together with the Yes-associated protein 1 (YAP1) co-activator. Indeed, inhibition of protein O-GlcNAcylation impedes their stability leading to decreased functionality of the BNC2/TEAD4/YAP1 complex towards promoting activation of the MF transcriptional regulatory landscape. We found that this involves O-GlcNAcylation of BNC2 at Thr(455) and Ser(490) and of TEAD4 at Ser(69) and Ser(99). Altogether, this study unravels protein O-GlcNAcylation as a key determinant of myofibroblastic activation and identifies its inhibition as an avenue to intervene with fibrogenic processes.},

note = {804},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{benazza_sec-ms_2024,

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

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

doi = {10.1016/j.talanta.2024.125727},

issn = {0039-9140},

year  = {2024},

date = {2024-05-01},

journal = {Talanta},

volume = {272},

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

note = {795},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{vaur_chemical_2024,

title = {Chemical Production of Cytotoxic Bispecific Antibodies Using the Ugi Multicomponent Reaction},

author = {V. Vaur and I. Koutsopetras and S. Erb and B. Jackowska and R. Benazza and H. Cahuzac and A. Detappe and O. Hernandez-Alba and S. Cianferani and C. J. Scott and G. Chaubet},

doi = {10.1002/cbic.202400170},

issn = {1439-7633 (ELECTRONIC) 1439-4227 (LINKING)},

year  = {2024},

date = {2024-05-01},

journal = {ChemBioChem},

pages = {e202400170},

abstract = {Bispecific antibodies (bsAbs) have recently emerged as a promising platform for the treatment of several conditions, most importantly cancer. Based on the combination of two different antigen-binding motifs in a single macromolecule; bsAbs can either display the combined characteristics of their parent antibodies, or new therapeutic features, inaccessible by the sole combination of two distinct antibodies. While bsAbs are traditionally produced by molecular biology techniques, the chemical development of bsAbs holds great promises and strategies have just begun to surface. In this context, we took advantage of a chemical strategy based on the use of the Ugi reaction for the site-selective conjugation of whole antibodies and coupled the resulting conjugates in a bioorthogonal manner with Fab fragments, derived from various antibodies. We thus managed to produce five different bsAbs with 2 : 1 valency, with yields ranging from 20 % to 48 %, and showed that the affinity of the parent antibody was preserved in all bsAbs. We further demonstrated the interest of our strategy by producing two other bsAbs behaving as cytotoxic T cell engagers with IC(50) values in the picomolar range in vitro.},

note = {805},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{del_giudice_ionic_2024,

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

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

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

issn = {1520-510X (ELECTRONIC) 0020-1669 (LINKING)},

year  = {2024},

date = {2024-04-01},

journal = {Inorg Chem},

volume = {63},

number = {13},

pages = {6103–6110},

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

note = {796},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{gizardin-fredon_denaturing_2024,

title = {Denaturing mass photometry for rapid optimization of chemical protein-protein cross-linking reactions},

author = {H. Gizardin-Fredon and P. E. Santo and M. E. Chagot and B. Charpentier and T. M. Bandeiras and X. Manival and O. Hernandez-Alba and S. Cianferani},

doi = {10.1038/s41467-024-47732-4},

issn = {2041-1723 (ELECTRONIC) 2041-1723 (LINKING)},

year  = {2024},

date = {2024-04-01},

journal = {Nat Commun},

volume = {15},

number = {1},

pages = {3516},

abstract = {Chemical cross-linking reactions (XL) are an important strategy for studying protein-protein interactions (PPIs), including low abundant sub-complexes, in structural biology. However, choosing XL reagents and conditions is laborious and mostly limited to analysis of protein assemblies that can be resolved using SDS-PAGE. To overcome these limitations, we develop here a denaturing mass photometry (dMP) method for fast, reliable and user-friendly optimization and monitoring of chemical XL reactions. The dMP is a robust 2-step protocol that ensures 95% of irreversible denaturation within only 5 min. We show that dMP provides accurate mass identification across a broad mass range (30 kDa-5 MDa) along with direct label-free relative quantification of all coexisting XL species (sub-complexes and aggregates). We compare dMP with SDS-PAGE and observe that, unlike the benchmark, dMP is time-efficient (3 min/triplicate), requires significantly less material (20-100x) and affords single molecule sensitivity. To illustrate its utility for routine structural biology applications, we show that dMP affords screening of 20 XL conditions in 1 h, accurately identifying and quantifying all coexisting species. Taken together, we anticipate that dMP will have an impact on ability to structurally characterize more PPIs and macromolecular assemblies, expected final complexes but also sub-complexes that form en route.},

note = {801},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{beauvieux_mesophotic_2024,

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

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

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

issn = {0722-4028},

year  = {2024},

date = {2024-03-01},

journal = {Coral Reefs},

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

note = {800},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{gomez-zepeda_thunder-dda-pasef_2024,

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

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

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

issn = {2041-1723 (ELECTRONIC) 2041-1723 (LINKING)},

year  = {2024},

date = {2024-03-01},

journal = {Nat Commun},

volume = {15},

number = {1},

pages = {2288},

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

note = {797},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{koutsopetras_site-selective_2024,

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

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

doi = {10.1002/chem.202303242},

issn = {1521-3765 (ELECTRONIC) 0947-6539 (LINKING)},

year  = {2024},

date = {2024-03-01},

journal = {Chemistry},

volume = {30},

number = {14},

pages = {e202303242},

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

note = {784},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{partiot_brain_2024,

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

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

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

issn = {2058-5276},

year  = {2024},

date = {2024-03-01},

journal = {Nature Microbiology},

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

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

note = {802},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{rady_targeted_2024,

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

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

doi = {10.1016/j.isci.2024.109068},

year  = {2024},

date = {2024-03-01},

journal = {Iscience},

volume = {27},

number = {3},

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

note = {799},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{becharguia_solution_2024,

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

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

doi = {10.1002/chem.202304131},

issn = {0947-6539},

year  = {2024},

date = {2024-02-01},

journal = {Chemistry-a European Journal},

volume = {30},

number = {12},

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

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

note = {794},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{trometer_synthesis_2024,

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

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

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

issn = {1520-6904 (ELECTRONIC) 0022-3263 (LINKING)},

year  = {2024},

date = {2024-02-01},

journal = {J Org Chem},

volume = {89},

number = {4},

pages = {2104–2126},

abstract = {This work describes the reactivity and properties of fluorinated derivatives (F-PD and F-PDO) of plasmodione (PD) and its metabolite, the plasmodione oxide (PDO). Introduction of a fluorine atom on the 2-methyl group markedly alters the redox properties of the 1,4-naphthoquinone electrophore, making the compound highly oxidizing and particularly photoreactive. A fruitful set of analytical methods (electrochemistry, absorption and emission spectrophotometry, and HRMS-ESI) have been used to highlight the products resulting from UV photoirradiation in the absence or presence of selected nucleophiles. With F-PDO and in the absence of nucleophile, photoreduction generates a highly reactive ortho-quinone methide (o-QM) capable of leading to the formation of a homodimer. In the presence of thiol nucleophiles such as beta-mercaptoethanol, which was used as a model, o-QMs are continuously regenerated in sequential photoredox reactions generating mono- or disulfanylation products as well as various unreported sulfanyl products. Besides, these photoreduced adducts derived from F-PDO are characterized by a bright yellowish emission due to an excited-state intramolecular proton transfer (ESIPT) process between the dihydronapthoquinone and benzoyl units. In order to evidence the possibility of an intramolecular coupling of the o-QM intermediate, a synthetic route to the corresponding anthrones is described. Tautomerization of the targeted anthrones occurs and affords highly fluorescent stable hydroxyl-anthraquinones. Although probable to explain the intense visible fluorescence emission also observed in tobacco BY-2 cells used as a cellular model, these coupling products have never been observed during the photochemical reactions performed in this study. Our data suggest that the observed ESIPT-induced fluorescence most likely corresponds to the generation of alkylated products through reduction species, as demonstrated with the beta-mercaptoethanol model. In conclusion, F-PDO thus acts as a novel (pro)-fluorescent probe for monitoring redox processes and protein alkylation in living cells.},

note = {791},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{cesar-rodo_regioselective_2024,

title = {Regioselective Synthesis of Potential Non-Quinonoid Prodrugs of Plasmodione: Antiparasitic Properties Against Two Hemoglobin-Feeding Parasites and Drug Metabolism Studies},

author = {Elena Cesar-Rodo and Baptiste Dupouy and Cécile Häberli and Jean-Marc Strub and David L. Williams and Pascal Mäser and Matthias Rottmann and Jennifer Keiser and Don Antoine Lanfranchi and Elisabeth Davioud-Charvet},

url = {https://www.mdpi.com/1420-3049/29/22/5268},

doi = {10.3390/molecules29225268},

issn = {1420-3049},

year  = {2024},

date = {2024-01-01},

urldate = {2025-01-07},

journal = {Molecules},

volume = {29},

number = {22},

pages = {5268},

abstract = {Ψ-1,4-naphthoquinones (Ψ-NQ) are non-quinoid compounds in which aromaticity—found in 1,4-naphthoquinones—is broken by the introduction of an angular methyl at C-4a or -8a. This series was designed to act as prodrugs of 1,4-naphthoquinones in an oxidative environment. Furthermore, from a medicinal chemistry point of view, the loss of planarity of the scaffold might lead to an improved solubility and circumvent the bad reputation of quinones in the pharmaceutical industry. In this work, we illustrated the concept by the synthesis of Ψ -plasmodione regioisomers as prodrugs of the antimalarial plasmodione. The presence of a chiral center introduces a new degree of freedom to be controlled by enantioselectivity and regioselectivity of the cycloaddition in the Diels–Alder reaction. The first strategy that was followed was based on the use of a chiral enantiopure sulfoxide to govern the stereoselective formation of (+)Ψ-NQ or (−)Ψ-NQ, depending on the chirality of the sulfoxide (R or S). New sulfinylquinones were synthesized but were found to be ineffective in undergoing cycloaddition with different dienes under a wide range of conditions (thermal, Lewis acid). The second strategy was based on the use of boronic acid-substituted benzoquinones as auxiliaries to control the regioselectivity. Using this methodology to prepare the (±)Ψ-NQ racemates, promising results (very fast cycloaddition time: textasciitilde2 h) were obtained with boronic acid-based quinones 25 and 27 in the presence of 1-methoxy-1,3-butadiene, to generate the 4a- and the 8a-Ψ-plasmodione regioisomers 1 and 2 (synthesized in six steps with a total yield of 10.5% and 4.1%, respectively. As the expected prodrug effect can only be revealed if the molecule undergoes an oxidation of the angular methyl, e.g., in blood-feeding parasites that digest hemoglobin from the host, the antimalarial and the antischistosomal properties of both (±)Ψ-NQ regioisomers were determined in drug assays with Plasmodium falciparum and Schistosoma mansoni. Metabolic studies under quasi-physiological conditions and LC-MS analyses were undertaken to reveal the generation of plasmodione from both the 4a- and the 8a-Ψ-plasmodione regioisomers.},

note = {826},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{hausmann_dataset_2024,

title = {A dataset profiling the multiomic landscape of the prefrontal cortex in amyotrophic lateral sclerosis},

author = {Fabian Hausmann and Lucas Caldi Gomes and Sonja Hänzelmann and Robin Khatri and Sergio Oller and Marie Gebelin and Mojan Parvaz and Laura Tzeplaeff and Laura Pasetto and Qihui Zhou and Pavol Zelina and Dieter Edbauer and R Jeroen Pasterkamp and Hubert Rehrauer and Ralph Schlapbach and Christine Carapito and Valentina Bonetto and Stefan Bonn and Paul Lingor},

url = {https://doi.org/10.1093/gigascience/giae100},

doi = {10.1093/gigascience/giae100},

issn = {2047-217X},

year  = {2024},

date = {2024-01-01},

urldate = {2025-01-06},

journal = {GigaScience},

volume = {13},

pages = {giae100},

abstract = {Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease, which still lacks effective disease-modifying therapies. Similar to other neurodegenerative disorders, such as Alzheimer and Parkinson disease, ALS pathology is presumed to propagate over time, originating from the motor cortex and spreading to other cortical regions. Exploring early disease stages is crucial to understand the causative molecular changes underlying the pathology. For this, we sampled human postmortem prefrontal cortex (PFC) tissue from Brodmann area 6, an area that exhibits only moderate pathology at the time of death, and performed a multiomic analysis of 51 patients with sporadic ALS and 50 control subjects. To compare sporadic disease to genetic ALS, we additionally analyzed PFC tissue from 4 transgenic ALS mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS) using the same methods. This multiomic data resource includes transcriptome, small RNAome, and proteome data from female and male samples, aimed at elucidating early and sex-specific ALS mechanisms, biomarkers, and drug targets.},

note = {808},

keywords = {},

pubstate = {published},

tppubtype = {article}

}