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  1. Article ; Online: Regulation of Endosomal Sorting and Maturation by ER-Endosome Contact Sites.

    Jean, Steve / Nassari, Sonya

    Contact (Thousand Oaks (Ventura County, Calif.))

    2022  Volume 5, Page(s) 25152564221106046

    Abstract: Endosomes are a heterogeneous population of intracellular organelles responsible for sorting, recycling, or transporting internalized materials for degradation. Endosomal sorting and maturation are controlled by a complex interplay of regulators, with ... ...

    Abstract Endosomes are a heterogeneous population of intracellular organelles responsible for sorting, recycling, or transporting internalized materials for degradation. Endosomal sorting and maturation are controlled by a complex interplay of regulators, with RAB GTPases and phosphoinositides playing key roles. In this decade, another layer of regulation surfaced with the role played by membrane contact sites between the endoplasmic reticulum (ER) and endosomes. Specific regulators of ER-endosome contact sites or proteins localized at these sites are emerging as modulators of this complex endosomal ballet. In particular, lipid transfer or recruitment of various complexes and enzymes at ER-endosome contact sites play an active role in endosome sorting, scission, and maturation. In this short review, we focus on studies describing ER-endosome contact sites in these three endosomal processes.
    Language English
    Publishing date 2022-06-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2964312-0
    ISSN 2515-2564 ; 2515-2564
    ISSN (online) 2515-2564
    ISSN 2515-2564
    DOI 10.1177/25152564221106046
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  2. Article ; Online: Autophagy in cell fate decisions: knowledge gained from

    Lacarrière-Keïta, Camille / Nassari, Sonya / Jean, Steve

    Genome

    2022  Volume 65, Issue 12, Page(s) 573–584

    Abstract: Autophagy is an important process that maintains adult tissue homeostasis and functions by protecting cells in autonomous and non-cell-autonomous ways. By degrading toxic components or proteins involved in cell signaling pathways, autophagy preserves the ...

    Abstract Autophagy is an important process that maintains adult tissue homeostasis and functions by protecting cells in autonomous and non-cell-autonomous ways. By degrading toxic components or proteins involved in cell signaling pathways, autophagy preserves the balance among stem cells, progenitors, and differentiated cells in various tissues. In this minireview, we discuss recent studies performed in
    MeSH term(s) Animals ; Drosophila/genetics ; Drosophila/metabolism ; Cell Differentiation ; Autophagy/genetics ; Stem Cells/metabolism ; Drosophila Proteins/genetics ; Drosophila Proteins/metabolism
    Chemical Substances Drosophila Proteins
    Language English
    Publishing date 2022-10-14
    Publishing country Canada
    Document type Journal Article ; Review
    ZDB-ID 639031-6
    ISSN 1480-3321 ; 0831-2796
    ISSN (online) 1480-3321
    ISSN 0831-2796
    DOI 10.1139/gen-2022-0069
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  3. Article ; Online: The Combination of Gold and Silver Food Nanoparticles with Gluten Peptides Alters the Autophagic Pathway in Intestinal Crypt-like Cells.

    Mancuso, Clara / Tremblay, Eric / Gnodi, Elisa / Jean, Steve / Beaulieu, Jean-François / Barisani, Donatella

    International journal of molecular sciences

    2023  Volume 24, Issue 17

    Abstract: Metallic nanoparticles (mNPs) are widely used as food additives and can interact with gliadin triggering an immune response, but evaluation of the effects on crypts, hypertrophic in celiac subjects, is still lacking. This study evaluated the effects of ... ...

    Abstract Metallic nanoparticles (mNPs) are widely used as food additives and can interact with gliadin triggering an immune response, but evaluation of the effects on crypts, hypertrophic in celiac subjects, is still lacking. This study evaluated the effects of gold and silver mNPs in combination with gliadin on crypt-like cells (HIEC-6). Transmission electron microscopy (TEM) was used to evaluate gliadin-mNP aggregates in cells. Western blot and immunofluorescence analysis assessed autophagy-related molecule levels (p62, LC3, beclin-1, EGFR). Lysosome functionality was tested with acridine orange (AO) and Magic Red assays. TEM identified an increase in autophagic vacuoles after exposure to gliadin + mNPs, as also detected by significant increments in LC3-II and p62 expression. Immunofluorescence confirmed the presence of mature autophagosomes, showing LC3 and p62 colocalization, indicating an altered autophagic flux, further assessed with EGFR degradation, AO and Magic Red assays. The results showed a significant reduction in lysosomal enzyme activity and a modest reduction in acidity. Thus, gliadin + mNPs can block the autophagic flux inducing a lysosomal defect. The alteration of this pathway, essential for cell function, can lead to cell damage and death. The potential effects of this copresence in food should be further characterized to avoid a negative impact on celiac disease subjects.
    MeSH term(s) Humans ; Gold ; Glutens ; Silver ; Gliadin ; Autophagy ; Acridine Orange ; Nanoparticles ; ErbB Receptors
    Chemical Substances Gold (7440-57-5) ; Glutens (8002-80-0) ; Silver (3M4G523W1G) ; Gliadin (9007-90-3) ; Acridine Orange (F30N4O6XVV) ; ErbB Receptors (EC 2.7.10.1)
    Language English
    Publishing date 2023-08-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms241713040
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  4. Article: Gemcitabine promotes autophagy and lysosomal function through ERK- and TFEB-dependent mechanisms.

    Marchand, Benoît / Poulin, Marc-Antoine / Lawson, Christine / Tai, Lee-Hwa / Jean, Steve / Boucher, Marie-Josée

    Cell death discovery

    2023  Volume 9, Issue 1, Page(s) 45

    Abstract: Gemcitabine is a first-line treatment agent for pancreatic ductal adenocarcinoma (PDAC). Contributing to its cytotoxicity, this chemotherapeutic agent is primarily a DNA replication inhibitor that also induces DNA damage. However, its therapeutic effects ...

    Abstract Gemcitabine is a first-line treatment agent for pancreatic ductal adenocarcinoma (PDAC). Contributing to its cytotoxicity, this chemotherapeutic agent is primarily a DNA replication inhibitor that also induces DNA damage. However, its therapeutic effects are limited owing to chemoresistance. Evidence in the literature points to a role for autophagy in restricting the efficacy of gemcitabine. Autophagy is a catabolic process in which intracellular components are delivered to degradative organelles lysosomes. Interfering with this process sensitizes PDAC cells to gemcitabine. It is consequently inferred that autophagy and lysosomal function need to be tightly regulated to maintain homeostasis and provide resistance to environmental stress, such as those imposed by chemotherapeutic drugs. However, the mechanism(s) through which gemcitabine promotes autophagy remains elusive, and the impact of gemcitabine on lysosomal function remains largely unexplored. Therefore, we applied complementary approaches to define the mechanisms triggered by gemcitabine that support autophagy and lysosome function. We found that gemcitabine elicited ERK-dependent autophagy in PDAC cells, but did not stimulate ERK activity or autophagy in non-tumoral human pancreatic epithelial cells. Gemcitabine also promoted transcription factor EB (TFEB)-dependent lysosomal function in PDAC cells. Indeed, treating PDAC cells with gemcitabine caused expansion of the lysosomal network, as revealed by Lysosome associated membrane protein-1 (LAMP1) and LysoTracker staining. More specific approaches have shown that gemcitabine promotes the activity of cathepsin B (CTSB), a cysteine protease playing an active role in lysosomal degradation. We showed that lysosomal function induced by gemcitabine depends on TFEB, the master regulator of autophagy and lysosomal biogenesis. Interfering with TFEB function considerably limited the clonogenic growth of PDAC cells and hindered the capacity of TFEB-depleted PDAC cells to develop orthotopic tumors.
    Language English
    Publishing date 2023-02-06
    Publishing country United States
    Document type Journal Article
    ISSN 2058-7716
    ISSN 2058-7716
    DOI 10.1038/s41420-023-01342-z
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  5. Article ; Online: La globalización, el quiebre de la generalidad ilusoria y la evolución de los emprendimientos ilícitos en Ecuador

    Javier Antonio Constantine Castro / María del Pilar Viteri Vera / Jean Steve Carrera López / Pedro Alfredo Huacon Cruz

    Encuentros, Vol

    2023  Volume 18

    Abstract: La globalización ha producido impactos transversales en la nociones cada vez más vacías pero mediáticamente espectaculares con las que se trata de autorepresentar la democracia ecuatoriana. La política, percibida como infinitamente corrupta, y su fracaso ...

    Abstract La globalización ha producido impactos transversales en la nociones cada vez más vacías pero mediáticamente espectaculares con las que se trata de autorepresentar la democracia ecuatoriana. La política, percibida como infinitamente corrupta, y su fracaso financiero, han abierto las puertas a emprendimientos ilícitos de alcance internaciona, que afectan la definición de un nuevo Estado. Consecuentemente, eestos emprendimientos se expresan con una abundante contundencia de realidad a través de delitos contra la vida y la integridad personal en las pentinenciarías, así como la ostentación del dinero consecunte del blanqueo, ante los ojos perplejos de la ciudadanía. Esto genera un efecto de realidad que se opone a la vacuidad de los discursos de las clases políticas y judiciales que representan la democracia. El artículo es un ensayo que basa su disertación en una revisión documental bibliográfica, empírica y criminológica sobre este fenómeno con el fin de establecer lo que se propone llamar el quiebre de la generalidad ilusoria en Ecuador, sugiriendo la aparición de un nuevo período histórico marcado por el delito.
    Keywords Emprendimientos ilícitos ; Globalización ; Delitos ; Generalidad Ilusoria ; History of scholarship and learning. The humanities ; AZ20-999 ; Social sciences (General) ; H1-99
    Language Spanish
    Publishing date 2023-05-01T00:00:00Z
    Publisher Universidad Nacional Experimental Rafael María Baralt
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Autophagic Flux Assessment in Colorectal Cancer Cells.

    Lauzier, Annie / Jean, Steve

    Methods in molecular biology (Clifton, N.J.)

    2018  Volume 1765, Page(s) 167–175

    Abstract: Autophagy protects colorectal cancer cells against therapeutic intervention. Autophagy is a continuous process, and autophagic flux requires both autophagosome synthesis and their subsequent degradation at lysosomes. Hence, cells with elevated autophagic ...

    Abstract Autophagy protects colorectal cancer cells against therapeutic intervention. Autophagy is a continuous process, and autophagic flux requires both autophagosome synthesis and their subsequent degradation at lysosomes. Hence, cells with elevated autophagic flux display both rapid autophagosome generation and degradation. Here, we describe an immunoblot protocol coupled to pharmaceutical inhibition of autophagosome clearance to monitor autophagic flux levels between colorectal cancer cell lines.
    MeSH term(s) Autophagy/drug effects ; Blotting, Western/instrumentation ; Blotting, Western/methods ; Cell Culture Techniques/instrumentation ; Cell Culture Techniques/methods ; Cell Line, Tumor ; Colorectal Neoplasms/pathology ; Humans ; Lipopeptides/metabolism ; Lysosomes/metabolism ; Lysosomes/pathology ; Macrolides/pharmacology ; Microtubule-Associated Proteins/analysis ; Microtubule-Associated Proteins/metabolism ; Phagosomes/metabolism ; Phagosomes/pathology
    Chemical Substances Lipopeptides ; MAP1LC3A protein, human ; MAP1LC3B protein, human ; Macrolides ; Microtubule-Associated Proteins ; bafilomycin A1 (88899-55-2)
    Language English
    Publishing date 2018-03-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-7765-9_10
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  7. Article ; Online: Rabs in Signaling and Embryonic Development.

    Nassari, Sonya / Del Olmo, Tomas / Jean, Steve

    International journal of molecular sciences

    2020  Volume 21, Issue 3

    Abstract: Rab GTPases play key roles in various cellular processes. They are essential, among other roles, to membrane trafficking and intracellular signaling events. Both trafficking and signaling events are crucial for proper embryonic development. Indeed, ... ...

    Abstract Rab GTPases play key roles in various cellular processes. They are essential, among other roles, to membrane trafficking and intracellular signaling events. Both trafficking and signaling events are crucial for proper embryonic development. Indeed, embryogenesis is a complex process in which cells respond to various signals and undergo dramatic changes in their shape, position, and function. Over the last few decades, cellular studies have highlighted the novel signaling roles played by Rab GTPases, while numerous studies have shed light on the important requirements of Rab proteins at various steps of embryonic development. In this review, we aimed to generate an overview of Rab contributions during animal embryogenesis. We first briefly summarize the involvement of Rabs in signaling events. We then extensively highlight the contribution of Rabs in shaping metazoan development and conclude with new approaches that will allow investigation of Rab functions in vivo.
    MeSH term(s) Animals ; Embryonic Development/physiology ; Humans ; Protein Transport/physiology ; Signal Transduction/physiology ; rab GTP-Binding Proteins/metabolism
    Chemical Substances rab GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2020-02-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms21031064
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  8. Article ; Online: Retraction: Pleiotropic role of Drosophila phosphoribosyl pyrophosphate synthetase in autophagy and lysosome homeostasis.

    Santos, Keemo Delos / Kim, Minhee / Yergeau, Christine / Jean, Steve / Moon, Nam-Sung

    PLoS genetics

    2022  Volume 18, Issue 2, Page(s) e1010048

    Language English
    Publishing date 2022-02-04
    Publishing country United States
    Document type Retraction of Publication
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1010048
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  9. Article ; Online: Rab21 in enterocytes participates in intestinal epithelium maintenance.

    Nassari, Sonya / Lacarrière-Keïta, Camille / Lévesque, Dominique / Boisvert, François-Michel / Jean, Steve

    Molecular biology of the cell

    2022  Volume 33, Issue 4, Page(s) ar32

    Abstract: Membrane trafficking is defined as the vesicular transport of proteins into, out of, and throughout the cell. In intestinal enterocytes, defects in endocytic/recycling pathways result in impaired function and are linked to diseases. However, how these ... ...

    Abstract Membrane trafficking is defined as the vesicular transport of proteins into, out of, and throughout the cell. In intestinal enterocytes, defects in endocytic/recycling pathways result in impaired function and are linked to diseases. However, how these trafficking pathways regulate intestinal tissue homeostasis is poorly understood. Using the
    MeSH term(s) Animals ; Autophagy ; Drosophila/metabolism ; Enterocytes/metabolism ; Intestinal Mucosa/metabolism ; rab GTP-Binding Proteins/metabolism
    Chemical Substances rab GTP-Binding Proteins (EC 3.6.5.2)
    Language English
    Publishing date 2022-02-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1098979-1
    ISSN 1939-4586 ; 1059-1524
    ISSN (online) 1939-4586
    ISSN 1059-1524
    DOI 10.1091/mbc.E21-03-0139
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2853: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
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    Zs.MO 410: Show issues

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  10. Article: RAB21 Activity Assay Using GST-fused APPL1.

    Jean, Steve / Kiger, Amy A

    Bio-protocol

    2017  Volume 6, Issue 4

    Abstract: The Rab family of small GTPases are essential regulators of membrane trafficking events. As with other small GTPase families, Rab GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. Guanine nucleotide exchange factors (GEFs) ... ...

    Abstract The Rab family of small GTPases are essential regulators of membrane trafficking events. As with other small GTPase families, Rab GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. Guanine nucleotide exchange factors (GEFs) promote Rab activation with the exchange of bound GDP for GTP, while GTPase-activating proteins (GAPs) regulate Rab inactivation with GTP hydrolysis. Numerous methods have been established to monitor the activation status of Rab GTPases. Of those, FRET-based methods are used to identify when and where a Rab GTPase is activated in cells. Unfortunately, the generation of such probes is complex, and only a limited number of Rabs have been probed this way. Biochemical purification of activated Rabs from cell or tissue extracts is easily achievable through the use of a known Rab effector domain to pull down a specific GTP-bound Rab form. Although this method is not ideal for detailed subcellular localization, it can offer temporal resolution of Rab activity. The identification of a growing number of specific effectors now allows tests for activation levels of many Rab GTPases in specific conditions. Here, we described an affinity purification approach using GST fused APPL1 (a known RAB21 effector) to test RAB21 activation in mammalian cells. This method was successfully used to assay changes in RAB21 activation status under nutrient rich versus starved conditions and to test the requirement of the MTMR13 RAB21 GEF in this process.
    Language English
    Publishing date 2017-02-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2833269-6
    ISSN 2331-8325
    ISSN 2331-8325
    DOI 10.21769/BioProtoc.1738
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