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Impaired mitochondrial function is a hallmark of aging and a major contributor to neurodegenerative diseases. We have shown that disrupted mitochondrial dynamics typically found in aging alters the fate of neural stem cells (NSCs) leading to impairments in learning and memory. At present, little is known regarding the mechanisms by which neural stem and progenitor cells survive and adapt to mitochondrial dysfunction. Using Opa1-inducible knockout as a model of aging and neurodegeneration, we identify a decline in neurogenesis due to impaired stem cell activation and progenitor proliferation, which can be rescued by the mitigation of oxidative stress through hypoxia. Through sc-RNA-seq, we identify the ATF4 pathway as a critical mechanism underlying cellular adaptation to metabolic stress. ATF4 knockdown in Opa1-deficient NSCs accelerates cell death, while the increased expression of ATF4 enhances proliferation and survival. Using a Slc7a11 mutant, an ATF4 target, we show that ATF4-mediated glutathione production plays a critical role in maintaining NSC survival and function under stress conditions. Together, we show that the activation of the integrated stress response (ISR) pathway enables NSCs to adapt to metabolic stress due to mitochondrial dysfunction and metabolic stress and may serve as a therapeutic target to enhance NSC survival and function in aging and neurodegeneration., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

As part of the culturomics project aiming at describing the human microbiota, we report in this study the description of the new bacterial genus Raoultibacter gen. nov. that includes two new species, that is, R. massiliensis sp. nov. and R. timonensis sp. nov. The R. massiliensis type strain Marseille-P2849 T was isolated from the fecal specimen of a healthy 19-year-old Saudi Bedouin, while R. timonensis type strain Marseille-P3277 T was isolated from the feces of an 11-year-old pygmy female living in Congo. Strain Marseille-P2849 T exhibited 91.4% 16S rRNA sequence similarity with Gordonibacter urolithinfaciens, its phylogenetic closest neighbor with standing in nomenclature. As well, strain Marseille-P3277 T exhibited 97.96% 16S rRNA similarity with strain Marseille-P2849 T . Both strains were Gram-positive, motile, nonspore-forming rod and form transparent microcolonies on blood agar in both anaerobic and microaerophilic atmospheres. The genome sizes of strain Marseille-P2849 T and strain Marseille-P3277 T were 3,657,161 bp and 4,000,215 bp, respectively. Using a taxono-genomic approach combining the phenotypic, biochemical, and genomic characteristics, we propose the genus Raoultibacter gen. nov., which contains strains Marseille-P2849 T (= CSUR P2849 T , = DSM 103407 T ) and Marseille-P3277 T (=CCUG 70680 T , =CSUR P3277 T ) as type strains of the species R. massiliensis sp. nov., and R. timonensis sp. nov., respectively., (© 2019 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

With the aim of describing the human microbiota by the means of culture methods, culturomics was developed in order to target previously un-isolated bacterial species and describe it via the taxono-genomics approach. While performing a descriptive study of the human gut microbiota of the pygmy people, strain Marseille-P4678 T has been isolated from a stool sample of a healthy 39-year-old pygmy male. Cells of this strain were Gram-positive cocci, spore-forming, non-motile, catalase-positive and oxidase-negative, and grow optimally at 37°C under anaerobic conditions. Its 16S rRNA gene sequence exhibited 89.69% of sequence similarity with Parvimonas micra strain 3119B T (NR 036934.1), its phylogenetically closest species with standing in nomenclature. The genome of strain Marseille-P4678 T is 2,083,161 long with 28.26 mol% of G+C content. Based on its phenotypic, biochemical, genotypic and proteomic profile, this bacterium was classified as a new bacterial genus and species Miniphocibacter massiliensis gen. nov., sp. nov. with the type strain Marseille-P4678 T ., (© 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Intensive efforts have been made to describe the human microbiome and its involvement in health and disease. Culturomics has been recently adapted to target formerly uncultured bacteria and other unclassified bacterial species. This approach enabled us to isolate in the current study a new bacterial species, Parabacteroides timonensis strain Marseille-P3236 T , from a stool sample of a healthy 39-year-old pygmy male. This strain, is an anaerobic, gram-negative, nonspore-forming motile rod. Its genome is made up of 6,483,434 bp with 43.41% G+C content, 5046 protein-encoding genes, and 84 RNA genes. We herein provide the full description of Parabacteroides timonensis strain Marseille-P3236 T through the taxonogenomic approach., (© 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Eggerthella timonensis strain Marseille-P3135 is a new bacterial species, isolated from the stool sample of a healthy 8-year-old pygmy female. This strain (LT598568) showed a 16S rRNA sequence similarity of 96.95% with its phylogenetically closest species with standing in nomenclature Eggerthella lenta strain DSM 2243 (AF292375). This bacterium is a nonspore forming, Gram-positive, nonmotile rod with catalase but no oxidase activity. Its genome is 3,916,897 bp long with 65.17 mol% of G + C content. Of the 3,371 predicted genes, 57 were RNAs and 3,314 were protein-coding genes. Here, we report the main phenotypic, biochemical, and genotypic characteristics of E. timonensis strain Marseille-P3135 (=CSUR P3135, =CCUG 70327); ti.mo.nen'sis, N.L. masc. adj., with timonensis referring to La Timone, which is the name of the hospital in Marseille (France) where this work was performed). Strain is a nonmotile Gram-positive rod, unable to sporulate, oxidase negative, and catalase positive. It grows under anaerobic conditions between 25°C and 42°C but optimally at 37°C., (© 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Using culturomics, a recently developed strategy based on diversified culture conditions for the isolation of previously uncultured bacteria, we isolated strain Marseille-P3296 T from a fecal sample of a healthy pygmy female. A multiphasic approach, taxono-genomics, was used to describe the major characteristics of this anaerobic and gram-positive bacillus that is unable to sporulate and is not motile. The genome of this bacterium is 1,878,572 bp-long with a 57.94 mol% G + C content. On the basis of these characteristics and after comparison with its closest phylogenetic neighbors, we are confident that strain Marseille-P3296 T (=CCUG 70328 =  CSUR P3296) is the type strain of a novel species for which we propose the name Collinsella bouchesdurhonensis sp. nov., (© 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)