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  • Springer Science and Business Media LLC  (5)
  • 1
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    Online Resource
    Mutational signatures association with replication timing in normal cells reveals similarities and differences with matched cancer tissues
    Springer Science and Business Media LLC ; 2023
    In:  Scientific Reports Vol. 13, No. 1 ( 2023-05-15)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-05-15)
    Abstract: Mutational signatures’ association with replication timing (RT) has been studied in cancer samples, but the RT distribution of somatic mutations in non-cancerous cells was only minimally explored. Here, we performed comprehensive analyses of mutational signatures in 2.9 million somatic mutations across multiple non-cancerous tissues, stratified by early and late RT regions. We found that many mutational processes are active mainly or solely in early RT, such as SBS16 in hepatocytes and SBS88 in the colon, or in late RT, such as SBS4 in lung and hepatocytes, and SBS18 across many tissues. The two ubiquitous signatures, SBS1 and SBS5, showed late and early bias, respectively, across multiple tissues and in mutations representing germ cells. We also performed a direct comparison with cancer samples in 4 matched tissue-cancer types. Unexpectedly, while for most signatures the RT bias was consistent in normal tissue and in cancer, we found that SBS1’s late RT bias is lost in cancer.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-023-34631-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2615211-3
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  • 2
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    3d $$ \mathcal{N} $$ = 4 OPE coefficients from Fermi gas
    Springer Science and Business Media LLC ; 2020
    In:  Journal of High Energy Physics Vol. 2020, No. 7 ( 2020-07)
    Details
    In: Journal of High Energy Physics, Springer Science and Business Media LLC, Vol. 2020, No. 7 ( 2020-07)
    Abstract: The partition function of a 3d $$ \mathcal{N} $$ N = 4 gauge theory with rank N can be computed using supersymmetric localization in terms of a matrix model, which often can be formulated as an ideal Fermi gas with a non-trivial one-particle Hamiltonian. We show how OPE coefficients of protected operators correspond in this formalism to averages of n -body operators in the Fermi gas, which can be computed to all orders in 1 /N using the WKB expansion. We use this formalism to compute OPE coefficients in the U( N ) k × U( N ) −k ABJM theory as well as the U( N ) theory with one adjoint and N f fundamental hypermultiplets, both of which have weakly coupled M-theory duals in the large N and finite k or N f regimes. For ABJM we reproduce known results, while for the N f theory we compute the all orders in 1 /N dependence at finite N f for the coefficient c T of the stress tensor two-point function.
    Type of Medium: Online Resource
    ISSN: 1029-8479
    URL: Article
    DOI: 10.1007/JHEP07(2020)041
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2027350-2
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  • 3
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    VPS4 is a dynamic component of the centrosome that regulates centrosome localization of γ-tubulin, centriolar satellite stability and ciliogenesis
    Springer Science and Business Media LLC ; 2018
    In:  Scientific Reports Vol. 8, No. 1 ( 2018-02-20)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2018-02-20)
    Abstract: The hexameric AAA ATPase VPS4 facilitates ESCRT III filament disassembly on diverse intracellular membranes. ESCRT III components and VPS4 have been localized to the ciliary transition zone and spindle poles and reported to affect centrosome duplication and spindle pole stability. How the canonical ESCRT pathway could mediate these events is unclear. We studied the association of VPS4 with centrosomes and found that GFP-VPS4 was a dynamic component of both mother and daughter centrioles. A mutant, VPS4 EQ , which can’t hydrolyze ATP, was less dynamic and accumulated at centrosomes. Centrosome localization of the VPS4 EQ mutant, caused reduced γ-tubulin levels at centrosomes and consequently decreased microtubule growth and altered centrosome positioning. In addition, preventing VPS4 ATP hydrolysis nearly eliminated centriolar satellites and paused ciliogensis after formation of the ciliary vesicle. Zebrafish embryos injected with GFP-VPS4 EQ mRNA were less viable, exhibited developmental defects and had fewer cilia in Kupffer’s vesicle. Surprisingly, ESCRT III proteins seldom localized to centrosomes and their depletion did not lead to these phenotypes. Our data support an ESCRT III-independent function for VPS4 at the centrosome and reveal that this evolutionary conserved AAA ATPase influences diverse centrosome functions and, as a result, global cellular architecture and development.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-018-21491-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2615211-3
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  • 4
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    Both cell autonomous and non-autonomous processes modulate the association between replication timing and mutation rate
    Springer Science and Business Media LLC ; 2023
    In:  Scientific Reports Vol. 13, No. 1 ( 2023-08-12)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-08-12)
    Abstract: Cancer somatic mutations are the product of multiple mutational and repair processes, some of which are tightly associated with DNA replication. Mutation rates (MR) are known to be higher in late replication timing (RT) regions, but different processes can affect this association. Systematic analysis of the mutational landscape of 2787 tumors from 32 tumor types revealed that approximately one third of the tumor samples show weak association between replication timing and mutation rate. Further analyses revealed that those samples have unique mutational signatures and are enriched with mutations in genes involved in DNA replication, DNA repair and chromatin structure. Surprisingly, analysis of differentially expressed genes between weak and strong RT-MR association groups revealed that tumors with weak association are enriched with genes associated with cell–cell communication and the immune system, suggesting a non-autonomous response to DNA damage.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-023-39463-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2615211-3
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  • 5
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    Online Resource
    Squashing, mass, and holography for 3d sphere free energy
    Springer Science and Business Media LLC ; 2021
    In:  Journal of High Energy Physics Vol. 2021, No. 4 ( 2021-04)
    Details
    In: Journal of High Energy Physics, Springer Science and Business Media LLC, Vol. 2021, No. 4 ( 2021-04)
    Abstract: We consider the sphere free energy F ( b ; m I ) in $$ \mathcal{N} $$ N = 6 ABJ(M) theory deformed by both three real masses m I and the squashing parameter b , which has been computed in terms of an N dimensional matrix model integral using supersymmetric localization. We show that setting $$ {m}_3=i\frac{b-{b}^{-1}}{2} $$ m 3 = i b − b − 1 2 relates F ( b ; m I ) to the round sphere free energy, which implies infinite relations between m I and b derivatives of F ( b ; m I ) evaluated at m I = 0 and b = 1. For $$ \mathcal{N} $$ N = 8 ABJ(M) theory, these relations fix all fourth order and some fifth order derivatives in terms of derivatives of m 1 , m 2 , which were previously computed to all orders in 1 /N using the Fermi gas method. This allows us to compute $$ {\partial}_b^4F\left|{}_{b=1}\right. $$ ∂ b 4 F b = 1 and $$ {\partial}_b^5F\left|{}_{b=1}\right. $$ ∂ b 5 F b = 1 to all orders in 1 /N , which we precisely match to a recent prediction to sub-leading order in 1 /N from the holographically dual AdS 4 bulk theory.
    Type of Medium: Online Resource
    ISSN: 1029-8479
    URL: Article
    DOI: 10.1007/JHEP04(2021)244
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2027350-2
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