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  1. Article ; Online: Activation of mTOR signaling in adult lung microvascular progenitor cells accelerates lung aging.

    Mason, Emma C / Menon, Swapna / Schneider, Benjamin R / Gaskill, Christa F / Dawson, Maggie M / Moore, Camille M / Armstrong, Laura Craig / Cho, Okyong / Richmond, Bradley W / Kropski, Jonathan A / West, James D / Geraghty, Patrick / Gomperts, Brigitte N / Ess, Kevin C / Gally, Fabienne / Majka, Susan M

    The Journal of clinical investigation

    2023  Volume 133, Issue 24

    Abstract: Reactivation and dysregulation of the mTOR signaling pathway are a hallmark of aging and chronic lung disease; however, the impact on microvascular progenitor cells (MVPCs), capillary angiostasis, and tissue homeostasis is unknown. While the existence of ...

    Abstract Reactivation and dysregulation of the mTOR signaling pathway are a hallmark of aging and chronic lung disease; however, the impact on microvascular progenitor cells (MVPCs), capillary angiostasis, and tissue homeostasis is unknown. While the existence of an adult lung vascular progenitor has long been hypothesized, these studies show that Abcg2 enriches for a population of angiogenic tissue-resident MVPCs present in both adult mouse and human lungs using functional, lineage, and transcriptomic analyses. These studies link human and mouse MVPC-specific mTORC1 activation to decreased stemness, angiogenic potential, and disruption of p53 and Wnt pathways, with consequent loss of alveolar-capillary structure and function. Following mTOR activation, these MVPCs adapt a unique transcriptome signature and emerge as a venous subpopulation in the angiodiverse microvascular endothelial subclusters. Thus, our findings support a significant role for mTOR in the maintenance of MVPC function and microvascular niche homeostasis as well as a cell-based mechanism driving loss of tissue structure underlying lung aging and the development of emphysema.
    MeSH term(s) Mice ; Humans ; Animals ; Lung/metabolism ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Stem Cells/metabolism ; Wnt Signaling Pathway ; Aging/genetics
    Chemical Substances TOR Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2023-12-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI171430
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Ua VI Zs.184: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Exposure to Propylparaben During Pregnancy and Lactation Induces Long-Term Alterations to the Mammary Gland in Mice.

    Mogus, Joshua P / LaPlante, Charlotte D / Bansal, Ruby / Matouskova, Klara / Schneider, Benjamin R / Daniele, Elizabeth / Silva, Shannon J / Hagen, Mary J / Dunphy, Karen A / Jerry, D Joseph / Schneider, Sallie S / Vandenberg, Laura N

    Endocrinology

    2021  Volume 162, Issue 6

    Abstract: The mammary gland is a hormone sensitive organ that is susceptible to endocrine-disrupting chemicals (EDCs) during the vulnerable periods of parous reorganization (ie, pregnancy, lactation, and involution). Pregnancy is believed to have long-term ... ...

    Abstract The mammary gland is a hormone sensitive organ that is susceptible to endocrine-disrupting chemicals (EDCs) during the vulnerable periods of parous reorganization (ie, pregnancy, lactation, and involution). Pregnancy is believed to have long-term protective effects against breast cancer development; however, it is unknown if EDCs can alter this effect. We examined the long-term effects of propylparaben, a common preservative used in personal care products and foods, with estrogenic properties, on the parous mouse mammary gland. Pregnant BALB/c mice were treated with 0, 20, 100, or 10 000 µg/kg/day propylparaben throughout pregnancy and lactation. Unexposed nulliparous females were also evaluated. Five weeks post-involution, mammary glands were collected and assessed for changes in histomorphology, hormone receptor expression, immune cell number, and gene expression. For several parameters of mammary gland morphology, propylparaben reduced the effects of parity. Propylparaben also increased proliferation, but not stem cell number, and induced modest alterations to expression of ERα-mediated genes. Finally, propylparaben altered the effect of parity on the number of several immune cell types in the mammary gland. These results suggest that propylparaben, at levels relevant to human exposure, can interfere with the effects of parity on the mouse mammary gland and induce long-term alterations to mammary gland structure. Future studies should address if propylparaben exposures negate the protective effects of pregnancy on mammary cancer development.
    MeSH term(s) Animals ; Cells, Cultured ; Endocrine Disruptors/toxicity ; Female ; Lactation/drug effects ; Male ; Mammary Glands, Animal/drug effects ; Mammary Glands, Animal/growth & development ; Mammary Glands, Animal/pathology ; Maternal Exposure/adverse effects ; Mice ; Mice, Inbred BALB C ; Parabens/toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects/chemically induced ; Prenatal Exposure Delayed Effects/pathology ; Prenatal Exposure Delayed Effects/physiopathology
    Chemical Substances Endocrine Disruptors ; Parabens ; propylparaben (Z8IX2SC1OH)
    Language English
    Publishing date 2021-03-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 427856-2
    ISSN 1945-7170 ; 0013-7227
    ISSN (online) 1945-7170
    ISSN 0013-7227
    DOI 10.1210/endocr/bqab041
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.72: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Manipulation of Fgf and Bmp signaling in teleost fishes suggests potential pathways for the evolutionary origin of multicuspid teeth.

    Jackman, William R / Davies, Shelby H / Lyons, David B / Stauder, Caitlin K / Denton-Schneider, Benjamin R / Jowdry, Andrea / Aigler, Sharon R / Vogel, Scott A / Stock, David W

    Evolution & development

    2014  Volume 15, Issue 2, Page(s) 107–118

    Abstract: Teeth with two or more cusps have arisen independently from an ancestral unicuspid condition in a variety of vertebrate lineages, including sharks, teleost fishes, amphibians, lizards, and mammals. One potential explanation for the repeated origins of ... ...

    Abstract Teeth with two or more cusps have arisen independently from an ancestral unicuspid condition in a variety of vertebrate lineages, including sharks, teleost fishes, amphibians, lizards, and mammals. One potential explanation for the repeated origins of multicuspid teeth is the existence of multiple adaptive pathways leading to them, as suggested by their different uses in these lineages. Another is that the addition of cusps required only minor changes in genetic pathways regulating tooth development. Here we provide support for the latter hypothesis by demonstrating that manipulation of the levels of Fibroblast growth factor (Fgf) or Bone morphogenetic protein (Bmp) signaling produces bicuspid teeth in the zebrafish (Danio rerio), a species lacking multicuspid teeth in its ancestry. The generality of these results for teleosts is suggested by the conversion of unicuspid pharyngeal teeth into bicuspid teeth by similar manipulations of the Mexican Tetra (Astyanax mexicanus). That these manipulations also produced supernumerary teeth in both species supports previous suggestions of similarities in the molecular control of tooth and cusp number. We conclude that despite their apparent complexity, the evolutionary origin of multicuspid teeth is positively constrained, likely requiring only slight modifications of a pre-existing mechanism for patterning the number and spacing of individual teeth.
    MeSH term(s) Animals ; Bone Morphogenetic Proteins/metabolism ; Characidae/genetics ; Characidae/growth & development ; Characidae/metabolism ; Evolution, Molecular ; Fibroblast Growth Factors/metabolism ; Fishes/classification ; Fishes/genetics ; Fishes/metabolism ; Pyrazoles/pharmacology ; Pyrimidines/pharmacology ; Signal Transduction ; Tooth/physiology ; Zebrafish/genetics ; Zebrafish/growth & development ; Zebrafish/metabolism
    Chemical Substances Bone Morphogenetic Proteins ; Pyrazoles ; Pyrimidines ; dorsomorphin (10K52CIC1Z) ; Fibroblast Growth Factors (62031-54-3)
    Language English
    Publishing date 2014-08-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2020288-X
    ISSN 1525-142X ; 1520-541X
    ISSN (online) 1525-142X
    ISSN 1520-541X
    DOI 10.1111/ede.12021
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity.

    McMullin, Ryan P / Wittner, Ben S / Yang, Chuanwei / Denton-Schneider, Benjamin R / Hicks, Daniel / Singavarapu, Raj / Moulis, Sharon / Lee, Jeongeun / Akbari, Mohammad R / Narod, Steven A / Aldape, Kenneth D / Steeg, Patricia S / Ramaswamy, Sridhar / Sgroi, Dennis C

    Breast cancer research : BCR

    2014  Volume 16, Issue 2, Page(s) R25

    Abstract: Introduction: There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal ... ...

    Abstract Introduction: There is an unmet clinical need for biomarkers to identify breast cancer patients at an increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with human epidermal growth factor receptor 2-positive (HER2+) brain metastasis.
    Methods: We combined laser capture microdissection and gene expression microarrays to analyze malignant epithelium from HER2+ breast cancer brain metastases with that from HER2+ nonmetastatic primary tumors. Differential gene expression was performed including gene set enrichment analysis (GSEA) using publicly available breast cancer gene expression data sets.
    Results: In a cohort of HER2+ breast cancer brain metastases, we identified a gene expression signature that anti-correlates with overexpression of BRCA1. Sequence analysis of the HER2+ brain metastases revealed no pathogenic mutations of BRCA1, and therefore the aforementioned signature was designated BRCA1 Deficient-Like (BD-L). Evaluation of an independent cohort of breast cancer metastases demonstrated that BD-L values are significantly higher in brain metastases as compared to other metastatic sites. Although the BD-L signature is present in all subtypes of breast cancer, it is significantly higher in BRCA1 mutant primary tumors as compared with sporadic breast tumors. Additionally, BD-L signature values are significantly higher in HER2-/ER- primary tumors as compared with HER2+/ER + and HER2-/ER + tumors. The BD-L signature correlates with breast cancer cell line pharmacologic response to a combination of poly (ADP-ribose) polymerase (PARP) inhibitor and temozolomide, and the signature outperformed four published gene signatures of BRCA1/2 deficiency.
    Conclusions: A BD-L signature is enriched in HER2+ breast cancer brain metastases without pathogenic BRCA1 mutations. Unexpectedly, elevated BD-L values are found in a subset of primary tumors across all breast cancer subtypes. Evaluation of pharmacological sensitivity in breast cancer cell lines representing all breast cancer subtypes suggests the BD-L signature may serve as a biomarker to identify sporadic breast cancer patients who might benefit from a therapeutic combination of PARP inhibitor and temozolomide and may be indicative of a dysfunctional BRCA1-associated pathway.
    MeSH term(s) Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; BRCA1 Protein/genetics ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; Brain Neoplasms/drug therapy ; Brain Neoplasms/genetics ; Brain Neoplasms/secondary ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Line ; Cell Line, Tumor ; DNA Damage ; DNA Mutational Analysis ; Dacarbazine/administration & dosage ; Dacarbazine/analogs & derivatives ; Enzyme Inhibitors/administration & dosage ; Enzyme Inhibitors/pharmacology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Immunohistochemistry ; Oligonucleotide Array Sequence Analysis ; Phthalazines/administration & dosage ; Piperazines/administration & dosage ; Poly(ADP-ribose) Polymerase Inhibitors ; Poly(ADP-ribose) Polymerases/genetics ; Poly(ADP-ribose) Polymerases/metabolism ; Prognosis ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Temozolomide ; Transcriptome
    Chemical Substances BRCA1 Protein ; Biomarkers, Tumor ; Enzyme Inhibitors ; Phthalazines ; Piperazines ; Poly(ADP-ribose) Polymerase Inhibitors ; Dacarbazine (7GR28W0FJI) ; Poly(ADP-ribose) Polymerases (EC 2.4.2.30) ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; olaparib (WOH1JD9AR8) ; Temozolomide (YF1K15M17Y)
    Language English
    Publishing date 2014-03-14
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2015059-3
    ISSN 1465-542X ; 1465-5411
    ISSN (online) 1465-542X
    ISSN 1465-5411
    DOI 10.1186/bcr3625
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5494: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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