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  1. Article: Impacts of white-tailed deer on regional patterns of forest tree recruitment

    Bradshaw, Lauren / Donald M. Waller

    Forest ecology and management. 2016 Sept. 01, v. 375

    2016  

    Abstract: Local, short- to medium-term studies make clear that white-tailed deer can greatly suppress tree growth and survival in palatable tree species. To assess how deer have broadly affected patterns of tree recruitment across northern Wisconsin, we analyzed ... ...

    Abstract Local, short- to medium-term studies make clear that white-tailed deer can greatly suppress tree growth and survival in palatable tree species. To assess how deer have broadly affected patterns of tree recruitment across northern Wisconsin, we analyzed recruitment success in 11 common trees species that vary in palatability across 13,105 USFS - FIA plots sampled between 1983 and 2013. We also examined how recruitment in these species covaried with estimated deer densities here. Saplings of five palatable species were scarce relative to less palatable species and showed highly skewed distributions. Scarcity and skew provide reliable signals of deer impacts even when deer have severely reduced recruitment and/or no reliable deer density data are available. Deer densities ranged from 2.3 to 23 deer per km2 over a 30year period. Sapling numbers in two maples (Acer) and aspen (Populus) with intermediate palatability declined sharply in apparent response to higher deer density. Path analysis also reveals that deer act to cumulatively depress sapling recruitment in these species over successive decades. Together, these approaches show that deer have strongly depressed sapling recruitment in all taxa except Abies and Picea. As these impacts are now propagating into larger sized trees, deer are also altering canopy composition and dynamics. The tools developed here provide efficient and reliable indicators for monitoring deer impacts on forest tree recruitment using consistent data collected by public agencies.
    Keywords Acer ; canopy ; data collection ; deer ; forest trees ; government agencies ; monitoring ; Odocoileus virginianus ; palatability ; Picea abies ; Populus ; saplings ; species recruitment ; tree growth ; Wisconsin
    Language English
    Dates of publication 2016-0901
    Size p. 1-11.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 751138-3
    ISSN 0378-1127
    ISSN 0378-1127
    DOI 10.1016/j.foreco.2016.05.019
    Database NAL-Catalogue (AGRICOLA)

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  2. Article: Combining the AKT inhibitor capivasertib and SERD fulvestrant is effective in palbociclib-resistant ER+ breast cancer preclinical models.

    Hopcroft, Lorna / Wigmore, Eleanor M / Williamson, Stuart C / Ros, Susana / Eberlein, Cath / Moss, Jennifer I / Urosevic, Jelena / Carnevalli, Larissa S / Talbot, Sara / Bradshaw, Lauren / Blaker, Catherine / Gunda, Sreeharsha / Owenson, Venetia / Hoffmann, Scott / Sutton, Daniel / Jones, Stewart / Goodwin, Richard J A / Willis, Brandon S / Rooney, Claire /
    de Bruin, Elza C / Barry, Simon T

    NPJ breast cancer

    2023  Volume 9, Issue 1, Page(s) 64

    Abstract: Combining the selective AKT inhibitor, capivasertib, and SERD, fulvestrant improved PFS in a Phase III clinical trial (CAPItello-291), treating HR+ breast cancer patients following aromatase inhibitors, with or without CDK4/6 inhibitors. However, ... ...

    Abstract Combining the selective AKT inhibitor, capivasertib, and SERD, fulvestrant improved PFS in a Phase III clinical trial (CAPItello-291), treating HR+ breast cancer patients following aromatase inhibitors, with or without CDK4/6 inhibitors. However, clinical data suggests CDK4/6 treatment may reduce response to subsequent monotherapy endocrine treatment. To support understanding of trials such as CAPItello-291 and gain insight into this emerging population of patients, we explored how CDK4/6 inhibitor treatment influences ER+ breast tumour cell function and response to fulvestrant and capivasertib after CDK4/6 inhibitor treatment. In RB+, RB- T47D and MCF7 palbociclib-resistant cells ER pathway ER and Greb-1 expression were reduced versus naïve cells. PI3K-AKT pathway activation was also modified in RB+ cells, with capivasertib less effective at reducing pS6 in RB+ cells compared to parental cells. Expression profiling of parental versus palbociclib-resistant cells confirmed capivasertib, fulvestrant and the combination differentially impacted gene expression modulation in resistant cells, with different responses seen in T47D and MCF7 cells. Fulvestrant inhibition of ER-dependent genes was reduced. In resistant cells, the combination was less effective at reducing cell cycle genes, but a consistent reduction in cell fraction in S-phase was observed in naïve and resistant cells. Despite modified signalling responses, both RB+ and RB- resistant cells responded to combination treatment despite some reduction in relative efficacy and was effective in vivo in palbociclib-resistant PDX models. Collectively these findings demonstrate that simultaneous inhibition of AKT and ER signalling can be effective in models representing palbociclib resistance despite changes in pathway dependency.
    Language English
    Publishing date 2023-08-05
    Publishing country United States
    Document type Journal Article
    ISSN 2374-4677
    ISSN 2374-4677
    DOI 10.1038/s41523-023-00571-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Author Correction: Combining the AKT inhibitor capivasertib and SERD fulvestrant is effective in palbociclib-resistant ER+ breast cancer preclinical models.

    Hopcroft, Lorna / Wigmore, Eleanor M / Williamson, Stuart C / Ros, Susana / Eberlein, Cath / Moss, Jennifer I / Urosevic, Jelena / Carnevalli, Larissa S / Talbot, Sara / Bradshaw, Lauren / Blaker, Catherine / Gunda, Sreeharsha / Owenson, Venetia / Hoffmann, Scott / Sutton, Daniel / Jones, Stewart / Goodwin, Richard J A / Willis, Brandon S / Rooney, Claire /
    DeBruin, Elza / Barry, Simon T

    NPJ breast cancer

    2023  Volume 9, Issue 1, Page(s) 69

    Language English
    Publishing date 2023-08-18
    Publishing country United States
    Document type Published Erratum
    ISSN 2374-4677
    ISSN 2374-4677
    DOI 10.1038/s41523-023-00575-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Author Correction: Combining the AKT inhibitor capivasertib and SERD fulvestrant is effective in palbociclib-resistant ER+ breast cancer preclinical models.

    Hopcroft, Lorna / Wigmore, Eleanor M / Williamson, Stuart C / Ros, Susana / Eberlein, Cath / Moss, Jennifer I / Urosevic, Jelena / Carnevalli, Larissa S / Talbot, Sara / Bradshaw, Lauren / Blaker, Catherine / Gunda, Sreeharsha / Owenson, Venetia / Hoffmann, Scott / Sutton, Daniel / Jones, Stewart / Goodwin, Richard J A / Willis, Brandon S / Rooney, Claire /
    de Bruin, Elza C / Barry, Simon T

    NPJ breast cancer

    2023  Volume 9, Issue 1, Page(s) 76

    Language English
    Publishing date 2023-09-19
    Publishing country United States
    Document type Published Erratum
    ISSN 2374-4677
    ISSN 2374-4677
    DOI 10.1038/s41523-023-00581-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Transcriptional Signatures of Tau and Amyloid Neuropathology.

    Castanho, Isabel / Murray, Tracey K / Hannon, Eilis / Jeffries, Aaron / Walker, Emma / Laing, Emma / Baulf, Hedley / Harvey, Joshua / Bradshaw, Lauren / Randall, Andrew / Moore, Karen / O'Neill, Paul / Lunnon, Katie / Collier, David A / Ahmed, Zeshan / O'Neill, Michael J / Mill, Jonathan

    Cell reports

    2020  Volume 30, Issue 6, Page(s) 2040–2054.e5

    Abstract: Alzheimer's disease (AD) is associated with the intracellular aggregation of hyperphosphorylated tau and the accumulation of β-amyloid in the neocortex. We use transgenic mice harboring human tau (rTg4510) and amyloid precursor protein (J20) mutations to ...

    Abstract Alzheimer's disease (AD) is associated with the intracellular aggregation of hyperphosphorylated tau and the accumulation of β-amyloid in the neocortex. We use transgenic mice harboring human tau (rTg4510) and amyloid precursor protein (J20) mutations to investigate transcriptional changes associated with the progression of tau and amyloid pathology. rTg4510 mice are characterized by widespread transcriptional differences in the entorhinal cortex with changes paralleling neuropathological burden across multiple brain regions. Differentially expressed transcripts overlap with genes identified in genetic studies of familial and sporadic AD. Systems-level analyses identify discrete co-expression networks associated with the progressive accumulation of tau that are enriched for genes and pathways previously implicated in AD pathology and overlap with co-expression networks identified in human AD cortex. Our data provide further evidence for an immune-response component in the accumulation of tau and reveal molecular pathways associated with the progression of AD neuropathology.
    MeSH term(s) Alzheimer Disease/genetics ; Amyloid beta-Peptides/adverse effects ; Animals ; Disease Models, Animal ; Disease Progression ; Humans ; Mice ; Mice, Transgenic ; tau Proteins/adverse effects
    Chemical Substances Amyloid beta-Peptides ; tau Proteins
    Language English
    Publishing date 2020-02-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2020.01.063
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Estradiol stabilizes the 105-kDa phospho-form of the adhesion docking protein NEDD9 and suppresses NEDD9-dependent cell spreading in breast cancer cells.

    Bradshaw, Lauren N / Zhong, J / Bradbury, P / Mahmassani, Maha / Smith, Jessica L / Ammit, Alaina J / O'Neill, Geraldine M

    Biochimica et biophysica acta

    2011  Volume 1813, Issue 2, Page(s) 340–345

    Abstract: Recent data suggest that the adhesion docking protein NEDD9/HEF1/Cas-L is a critical regulator of adhesion-dependent signalling pathways during mammary tumour development. Multiple phosphorylation modifications of NEDD9 regulate interaction with ... ...

    Abstract Recent data suggest that the adhesion docking protein NEDD9/HEF1/Cas-L is a critical regulator of adhesion-dependent signalling pathways during mammary tumour development. Multiple phosphorylation modifications of NEDD9 regulate interaction with downstream protein partners, thus the regulation of NEDD9 phospho-forms is an important point of control for NEDD9 function. As estradiol (E2) plays a central role in the development and progression of breast cancer, we have investigated NEDD9 phospho-form regulation in MCF-7 estrogen receptor (ER)-positive breast cancer cells in response to estrogen. We find that levels of the 105-kDa NEDD9 phospho-form are significantly increased after 3days of estrogen exposure, and this is suppressed by the anti-estrogen tamoxifen. Analysis of protein decay kinetics following treatment with the protein synthesis inhibitor cycloheximide indicates that increased 105-kDa levels are due to a slower rate of protein decay. Moreover, exogenous expression of NEDD9 failed to induce spreading in the presence of E2, and this was reversed by tamoxifen treatment. Finally, we show that the 105-kDa NEDD9 phospho-form appears to predominate in ER-positive versus ER-negative breast cancer cell lines. Taken together, our results suggest that estradiol may suppress phospho-form-specific functions of NEDD9.
    MeSH term(s) Adaptor Proteins, Signal Transducing/metabolism ; Antineoplastic Agents, Hormonal/pharmacology ; Blotting, Western ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Adhesion/drug effects ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Estradiol/pharmacology ; Female ; Humans ; Phosphoproteins/metabolism ; Phosphorylation/drug effects ; Receptors, Estrogen/metabolism ; Signal Transduction/drug effects ; Tamoxifen/pharmacology ; Tumor Cells, Cultured
    Chemical Substances Adaptor Proteins, Signal Transducing ; Antineoplastic Agents, Hormonal ; NEDD9 protein, human ; Phosphoproteins ; Receptors, Estrogen ; Tamoxifen (094ZI81Y45) ; Estradiol (4TI98Z838E)
    Language English
    Publishing date 2011-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 60-7
    ISSN 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    ISSN (online) 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
    ISSN 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
    DOI 10.1016/j.bbamcr.2010.11.018
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Estradiol stabilizes the 105-kDa phospho-form of the adhesion docking protein NEDD9 and suppresses NEDD9-dependent cell spreading in breast cancer cells

    Bradshaw, Lauren N / Zhong, J / Bradbury, P / Mahmassani, Maha / Smith, Jessica L / Ammit, Alaina J / O'Neill, Geraldine M

    Biochimica et biophysica acta. Molecular cell research. 2011 Feb., v. 1813, no. 2

    2011  

    Abstract: Recent data suggest that the adhesion docking protein NEDD9/HEF1/Cas-L is a critical regulator of adhesion-dependent signalling pathways during mammary tumour development. Multiple phosphorylation modifications of NEDD9 regulate interaction with ... ...

    Abstract Recent data suggest that the adhesion docking protein NEDD9/HEF1/Cas-L is a critical regulator of adhesion-dependent signalling pathways during mammary tumour development. Multiple phosphorylation modifications of NEDD9 regulate interaction with downstream protein partners, thus the regulation of NEDD9 phospho-forms is an important point of control for NEDD9 function. As estradiol (E2) plays a central role in the development and progression of breast cancer, we have investigated NEDD9 phospho-form regulation in MCF-7 estrogen receptor (ER)-positive breast cancer cells in response to estrogen. We find that levels of the 105-kDa NEDD9 phospho-form are significantly increased after 3days of estrogen exposure, and this is suppressed by the anti-estrogen tamoxifen. Analysis of protein decay kinetics following treatment with the protein synthesis inhibitor cycloheximide indicates that increased 105-kDa levels are due to a slower rate of protein decay. Moreover, exogenous expression of NEDD9 failed to induce spreading in the presence of E2, and this was reversed by tamoxifen treatment. Finally, we show that the 105-kDa NEDD9 phospho-form appears to predominate in ER-positive versus ER-negative breast cancer cell lines. Taken together, our results suggest that estradiol may suppress phospho-form-specific functions of NEDD9.
    Keywords adhesion ; breast neoplasms ; cycloheximide ; estradiol ; estrogen receptors ; mammary neoplasms (animal) ; neoplasm cells ; phosphorylation ; protein synthesis inhibitors ; signal transduction ; tamoxifen
    Language English
    Dates of publication 2011-02
    Size p. 340-345.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 283444-3
    ISSN 0167-4889
    ISSN 0167-4889
    DOI 10.1016/j.bbamcr.2010.11.018
    Database NAL-Catalogue (AGRICOLA)

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