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Article ; Online: Mass spectrometry-based intraoperative tumor diagnostics

Isabelle Fournier / Michel Salzet

Future Science OA, Vol 5, Iss

a letter in reply

2019 Volume 7

Keywords	cancer ; guided surgery ; intraoperative tumor diagnostics ; real-time diagnosis ; SpiderMass ; surgery ; Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2019-08-01T00:00:00Z
Publisher	Future Science Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Unveiling a Ghost Proteome in the Glioblastoma Non-Coding RNAs

Tristan Cardon / Isabelle Fournier / Michel Salzet

Frontiers in Cell and Developmental Biology, Vol

2021 Volume 9

Abstract: Glioblastoma is the most common brain cancer in adults. Nevertheless, the median survival time is 15 months, if treated with at least a near total resection and followed by radiotherapy in association with temozolomide. In glioblastoma (GBM), variations ... ...

Abstract	Glioblastoma is the most common brain cancer in adults. Nevertheless, the median survival time is 15 months, if treated with at least a near total resection and followed by radiotherapy in association with temozolomide. In glioblastoma (GBM), variations of non-coding ribonucleic acid (ncRNA) expression have been demonstrated in tumor processes, especially in the regulation of major signaling pathways. Moreover, many ncRNAs present in their sequences an Open Reading Frame (ORF) allowing their translations into proteins, so-called alternative proteins (AltProt) and constituting the “ghost proteome.” This neglected world in GBM has been shown to be implicated in protein–protein interaction (PPI) with reference proteins (RefProt) reflecting involvement in signaling pathways linked to cellular mobility and transfer RNA regulation. More recently, clinical studies have revealed that AltProt is also involved in the patient’s survival and bad prognosis. We thus propose to review the ncRNAs involved in GBM and highlight their function in the disease.
Keywords	alternative proteins ; glioblastoma ; LncRNA—long noncoding RNA ; SEPs ; ncRNA (noncoding RNA) ; brain cancer ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-12-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protocol to identify human subcellular alternative protein interactions using cross-linking mass spectrometry

Diego Fernando Garcia-del Rio / Isabelle Fournier / Tristan Cardon / Michel Salzet

STAR Protocols, Vol 4, Iss 3, Pp 102380- (2023)

2023

Abstract: Summary: Since the start of mass-spectrometry-based proteomics, proteins from non-referenced open reading frames or alternative proteins (AltProts) have been overlooked. Here, we present a protocol to identify human subcellular AltProt and decipher some ... ...

Abstract	Summary: Since the start of mass-spectrometry-based proteomics, proteins from non-referenced open reading frames or alternative proteins (AltProts) have been overlooked. Here, we present a protocol to identify human subcellular AltProt and decipher some interactions using cross-linking mass spectrometry. We describe steps for cell culture, in cellulo cross-link, subcellular extraction, and sequential digestion. We then detail both liquid chromatography-tandem mass spectrometry and cross-link data analyses. The implementation of a single workflow allows the non-targeted identification of signaling pathways involving AltProts.For complete details on the use and execution of this protocol, please refer to Garcia-del Rio et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
Keywords	Bioinformatics ; Proteomics ; Mass Spectrometry ; Systems Biology ; Science (General) ; Q1-390
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: SARS-Cov-2 Interactome with Human Ghost Proteome

Tristan Cardon / Isabelle Fournier / Michel Salzet

Microorganisms, Vol 8, Iss 2036, p

A Neglected World Encompassing a Wealth of Biological Data

2020 Volume 2036

Abstract: Conventionally, eukaryotic mRNAs were thought to be monocistronic, leading to the translation of a single protein. However, large-scale proteomics have led to a massive identification of proteins translated from mRNAs of alternative ORF (AltORFs), in ... ...

Abstract	Conventionally, eukaryotic mRNAs were thought to be monocistronic, leading to the translation of a single protein. However, large-scale proteomics have led to a massive identification of proteins translated from mRNAs of alternative ORF (AltORFs), in addition to the predicted proteins issued from the reference ORF or from ncRNAs. These alternative proteins (AltProts) are not represented in the conventional protein databases and this “ghost proteome” was not considered until recently. Some of these proteins are functional and there is growing evidence that they are involved in central functions in physiological and physiopathological context. Based on our experience with AltProts, we were interested in finding out their interaction with the viral protein coming from the SARS-CoV-2 virus, responsible for the 2020 COVID-19 outbreak. Thus, we have scrutinized the recently published data by Krogan and coworkers (2020) on the SARS-CoV-2 interactome with host cells by affinity purification in co-immunoprecipitation (co-IP) in the perspective of drug repurposing. The initial work revealed the interaction between 332 human cellular reference proteins (RefProts) with the 27 viral proteins. Re-interrogation of this data using 23 viral targets and including AltProts, followed by enrichment of the interaction networks, leads to identify 218 RefProts (in common to initial study), plus 56 AltProts involved in 93 interactions. This demonstrates the necessity to take into account the ghost proteome for discovering new therapeutic targets, and establish new therapeutic strategies. Missing the ghost proteome in the drug metabolism and pharmacokinetic (DMPK) drug development pipeline will certainly be a major limitation to the establishment of efficient therapies.
Keywords	SARS-Cov-2 ; interactomics ; ghost protein ; drug repurposing ; Alternative protein ; non-coding RNA ; Biology (General) ; QH301-705.5
Subject code	570 ; 572
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Establishment and characterization of canine mammary tumoroids for translational research

Antonella Raffo-Romero / Soulaimane Aboulouard / Emmanuel Bouchaert / Agata Rybicka / Dominique Tierny / Nawale Hajjaji / Isabelle Fournier / Michel Salzet / Marie Duhamel

BMC Biology, Vol 21, Iss 1, Pp 1-

2023 Volume 19

Abstract: Abstract Background Cancer heterogeneity is a main obstacle for the development of effective therapies, as its replication in in vitro preclinical models is challenging. Around 96% of developed drugs are estimated to fail from discovery to the clinical ... ...

Abstract	Abstract Background Cancer heterogeneity is a main obstacle for the development of effective therapies, as its replication in in vitro preclinical models is challenging. Around 96% of developed drugs are estimated to fail from discovery to the clinical trial phase probably because of the unsuitability and unreliability of current preclinical models (Front Pharmacol 9:6, 2018; Nat Rev Cancer 8: 147–56, 2008) in replicating the overall biology of tumors, for instance the tumor microenvironment. Breast cancer is the most frequent cancer among women causing the greatest number of cancer-related deaths. Breast cancer can typically be modeled in vitro through the use of tumoroids; however, current approaches using mouse tumoroids fail to reproduce crucial aspect of human breast cancer, while access to human cells is limited and the focus of ethical concerns. New models of breast cancer, such as companion dogs, have emerged given the resemblance of developed spontaneous mammary tumors to human breast cancer in many clinical and molecular aspects; however, they have so far failed to replicate the tumor microenvironment. The present work aimed at developing a robust canine mammary tumor model in the form of tumoroids which recapitulate the tumor diversity and heterogeneity. Results We conducted a complete characterization of canine mammary tumoroids through histologic, molecular, and proteomic analysis, demonstrating their strong similarity to the primary tumor. We demonstrated that these tumoroids can be used as a drug screening model. In fact, we showed that paclitaxel, a human chemotherapeutic, could kill canine tumoroids with the same efficacy as human tumoroids with 0.1 to 1 μM of drug needed to kill 50% of the cells. Due to easy tissue availability, canine tumoroids can be produced at larger scale and cryopreserved to constitute a biobank. We have demonstrated that cryopreserved tumoroids keep the same histologic and molecular features (ER, PR, and HER2 expression) as fresh tumoroids. Furthermore, two ...
Keywords	Breast cancer ; Dog patients ; Tumoroid ; Biobank ; Drug screening ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Neuro-immune lessons from an annelid: The medicinal leech

Tasiemski, Aurélie / Michel Salzet

Developmental and comparative immunology. 2017 Jan., v. 66

2017

Abstract: An important question that remains unanswered is how the vertebrate neuroimmune system can be both friend and foe to the damaged nervous tissue. Some of the difficulty in obtaining responses in mammals probably lies in the conflation in the central ... ...

Abstract	An important question that remains unanswered is how the vertebrate neuroimmune system can be both friend and foe to the damaged nervous tissue. Some of the difficulty in obtaining responses in mammals probably lies in the conflation in the central nervous system (CNS), of the innate and adaptive immune responses, which makes the vertebrate neuroimmune response quite complex and difficult to dissect. An alternative strategy for understanding the relation between neural immunity and neural repair is to study an animal devoid of adaptive immunity and whose CNS is well described and regeneration competent. The medicinal leech offers such opportunity. If the nerve cord of this annelid is crushed or partially cut, axons grow across the lesion and conduction of signals through the damaged region is restored within a few days, even when the nerve cord is removed from the animal and maintained in culture. When the mammalian spinal cord is injured, regeneration of normal connections is more or less successful and implies multiple events that still remain difficult to resolve. Interestingly, the regenerative process of the leech lesioned nerve cord is even more successful under septic than under sterile conditions suggesting that a controlled initiation of an infectious response may be a critical event for the regeneration of normal CNS functions in the leech. Here are reviewed and discussed data explaining how the leech nerve cord sensu stricto (i.e. excluding microglia and infiltrated blood cells) recognizes and responds to microbes and mechanical damages.
Keywords	adaptive immunity ; Annelida ; aseptic conditions ; axons ; blood cells ; mammals ; microorganisms ; nerve tissue ; neuroglia ; spinal cord
Language	English
Dates of publication	2017-01
Size	p. 33-42.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2016.06.026
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Canine Bone Marrow Mesenchymal Stem Cell Conditioned Media Affect Bacterial Growth, Biofilm-Associated Staphylococcus aureus and AHL-Dependent Quorum Sensing

Dobroslava Bujňáková / Anna Čuvalová / Milan Čížek / Filip Humenik / Michel Salzet / Daša Čížková

Microorganisms, Vol 8, Iss 1478, p

2020 Volume 1478

Abstract: The present study investigated the in vitro antibacterial, antibiofilm and anti-Quorum Sensing (anti-QS) activities of canine bone marrow mesenchymal stem cell-conditioned media (cBM MSC CM) containing all secreted factors <30 K, using a disc diffusion ... ...

Abstract	The present study investigated the in vitro antibacterial, antibiofilm and anti-Quorum Sensing (anti-QS) activities of canine bone marrow mesenchymal stem cell-conditioned media (cBM MSC CM) containing all secreted factors <30 K, using a disc diffusion test (DDT), spectrophotometric Crystal Violet Assay (SCVA) and Bioluminescence Assay (BA) with QS-reporter Escherichia coli JM109 pSB1142. The results show a sample-specific bacterial growth inhibition (zones varied between 7–30 mm), statistically significant modulation of biofilm-associated Staphylococcus aureus and Escherichia coli bioluminescence (0.391 ± 0.062 in the positive control to the lowest 0.150 ± 0.096 in the experimental group, cf. 11,714 ± 1362 to 7753 ± 700, given as average values of absorbance A 550 ± SD versus average values of relative light units to growth RLU/A 550 ± SD). The proteomic analysis performed in our previous experiment revealed the presence of several substances with documented antibacterial, antibiofilm and immunomodulatory properties (namely, apolipoprotein B and D; amyloid-β peptide; cathepsin B; protein S100-A4, galectin 3, CLEC3A , granulin, transferrin). This study highlights that cBM MSC CM may represent an important new approach to managing biofilm-associated and QS signal molecule-dependent bacterial infections. To the best of our knowledge, there is no previous documentation of canine BM MSC CM associated with in vitro antibiofilm and anti-QS activity.
Keywords	quorum sensing ; biofilm ; Escherichia coli JM109 pSB1142 ; mesenchymal stem cells ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protein Kinase C Activation Drives a Differentiation Program in an Oligodendroglial Precursor Model through the Modulation of Specific Biological Networks

Marina Damato / Tristan Cardon / Maxence Wisztorski / Isabelle Fournier / Damiana Pieragostino / Ilaria Cicalini / Michel Salzet / Daniele Vergara / Michele Maffia

International Journal of Molecular Sciences, Vol 22, Iss 5245, p

2021 Volume 5245

Abstract: Protein kinase C (PKC) activation induces cellular reprogramming and differentiation in various cell models. Although many effectors of PKC physiological actions have been elucidated, the molecular mechanisms regulating oligodendrocyte differentiation ... ...

Abstract	Protein kinase C (PKC) activation induces cellular reprogramming and differentiation in various cell models. Although many effectors of PKC physiological actions have been elucidated, the molecular mechanisms regulating oligodendrocyte differentiation after PKC activation are still unclear. Here, we applied a liquid chromatography–mass spectrometry (LC–MS/MS) approach to provide a comprehensive analysis of the proteome expression changes in the MO3.13 oligodendroglial cell line after PKC activation. Our findings suggest that multiple networks that communicate and coordinate with each other may finally determine the fate of MO3.13 cells, thus identifying a modular and functional biological structure. In this work, we provide a detailed description of these networks and their participating components and interactions. Such assembly allows perturbing each module, thus describing its physiological significance in the differentiation program. We applied this approach by targeting the Rho-associated protein kinase (ROCK) in PKC-activated cells. Overall, our findings provide a resource for elucidating the PKC-mediated network modules that contribute to a more robust knowledge of the molecular dynamics leading to this cell fate transition.
Keywords	PKC ; differentiation ; oligodendrocytes ; signaling ; mass spectrometry ; cytoskeleton ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	612
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Cumulative learning enables convolutional neural network representations for small mass spectrometry data classification

Khawla Seddiki / Philippe Saudemont / Frédéric Precioso / Nina Ogrinc / Maxence Wisztorski / Michel Salzet / Isabelle Fournier / Arnaud Droit

Nature Communications, Vol 11, Iss 1, Pp 1-

2020 Volume 11

Abstract: Convolutional Neural Networks are powerful tools for clinical diagnosis but their effectiveness decreases when the number of available samples is small. Here, the authors develop a cumulative learning method by training the same model through several ... ...

Abstract	Convolutional Neural Networks are powerful tools for clinical diagnosis but their effectiveness decreases when the number of available samples is small. Here, the authors develop a cumulative learning method by training the same model through several classification tasks over various small Mass Spectrometry datasets.
Keywords	Science ; Q
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular Mapping of Hydrogen Sulfide Targets in Normal Human Keratinocytes

Olivia Gross-Amat / Marine Guillen / Jean-Pascal Gimeno / Michel Salzet / Nicolas Lebonvallet / Laurent Misery / Céline Auxenfans / Serge Nataf

International Journal of Molecular Sciences, Vol 21, Iss 4648, p

2020 Volume 4648

Abstract: Although sulfur-rich thermal waters have ancestrally been used in the context of dermatological conditions, a global mapping of the molecular effects exerted by H 2 S on human keratinocytes is still lacking. To fill this knowledge gap, we subjected ... ...

Abstract	Although sulfur-rich thermal waters have ancestrally been used in the context of dermatological conditions, a global mapping of the molecular effects exerted by H 2 S on human keratinocytes is still lacking. To fill this knowledge gap, we subjected cultured human keratinocytes to distinct amounts of the non-gaseous hydrogen sulfur donor NaHS. We first checked that H 2 S accumulated in the cytoplasm of keratinocytes under our experimental conditions andused a combination of proteomics, genomics and biochemical approaches to unravel functionally relevant H 2 S targets in human keratinocytes. We found that the identified targets fall into two main categories: (i) the oxidative stress response molecules superoxide dismutase 2 (SOD2), NAD(P)H quinone dehydrogenase 1 (NQO1) and culin 3 (CUL3) and (ii) the chemokines interleukin-8 (IL-8) and CXCL2. Interestingly, NaHS also stimulated the caspase-1 inflammasome pathway, leading to increased secretion of the pro-inflammatory molecule interleukin-18 (IL-18). Interestingly, the secretion of interleukin-1 beta (IL-1β) was only modestly impacted by NaHS exposure despite a significant accumulation of IL-1β pro-form. Finally, we observed that NaHS significantly hampered the growth of human keratinocyte progenitors and stem cells cultured under clonogenic conditions or as epidermal cell sheets. We conclude that H 2 S exerts specific molecular effects on normal human keratinocytes.
Keywords	human keratinocyte ; H2S ; RNAseq ; proteomics ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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