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RNA binding protein (RBPs) and microRNAs (miRNAs or miRs) are post-transcriptional regulators of gene expression that are implicated in development of cancers. Although their individual roles have been studied, the crosstalk between RBPs and miRNAs is under intense investigation. Here, we show that in breast cancer cells, cyclin E1 upregulation by the RBP HuR is through specific binding to regions in the cyclin E1 mRNA 3' untranslated region (3'UTR) containing U-rich elements. Similarly, miR-16 represses cyclin E1, dependent on its cognate binding sites in the cyclin E1 3'UTR. Evidence in the literature indicates that HuR can regulate miRNA expression and recruit or dissociate RNA-induced silencing complexes (RISC). Despite this, miR-16 and HuR do not affect the other's expression level or binding to the cyclin E1 3'UTR. While HuR overexpression partially blocks miR-16 repression of a reporter mRNA containing the cyclin E1 3'UTR, it does not block miR-16 repression of endogenous cyclin E1 mRNA. In contrast, miR-16 blocks HuR-mediated upregulation of cyclin E1. Overall our results suggest that miR-16 can override HuR upregulation of cyclin E1 without affecting HuR expression or association with the cyclin E1 mRNA.

RNA binding proteins (RBPs) post-transcriptionally regulate gene expression by associating with regulatory sequences in the untranslated regions of mRNAs. Cold-inducible RBP (CIRP) is a stress-induced RBP that was recently shown to modulate inflammation in response to cellular stress, where it increases or decreases pro-tumorigenic (proinflammatory) cytokines in different contexts. CIRP expression is altered in several cancers, including breast cancer, but the effects of CIRP on inflammation in breast cancer is not known. Here, we investigate if CIRP alters growth and the inflammatory profile of breast tumors. Transgenic mice overexpressing CIRP in the mammary epithelium were crossed with the PyMT mouse model of breast cancer, and the effects on both early and late tumorigenesis and inflammation were assessed. The effects of CIRP knockdown were also assessed in Py2T cell grafts. Overexpression of CIRP led to decreased tumorigenesis in the PyMT mouse model. Conversely, the knockdown of CIRP in Py2T cell grafts led to increased tumor growth. Luminex cytokine assays assessed the effects on the inflammatory environment. CIRP/PyMT mammary glands/mammary tumors and serum had decreased cytokines that promote inflammation, angiogenesis, and metastasis compared to PyMT mammary glands and serum, documenting a shift towards an environment less supportive of tumorigenesis. CIRP overexpression also decreased CD4 helper T cells and increased CD8 cytotoxic T cells in mammary tumors. Overall, these data support a role for CIRP as a potent antitumor molecule that suppresses both local and systemic pro-tumorigenic inflammation.

We recorded Bushtit (Psaltriparus minimus) flock size on the Seattle University campus across multiple seasons in order to characterize the timing of pair formation prior to nest building in Washington state and compare it to that of California and Arizona. We also collected autumn and winter foraging locations, specifically vegetation types and foraging heights. We found the disbanding of large flocks (15–20 birds) into nest-building pairs occurred 1–2 months later in the northern part of the Bushtit's range than what is reported in more southern states. Bushtits spent a similar percentage of time foraging in deciduous trees, evergreen trees, and mixed shrubs in fall and winter, often moving along garden strips at heights of 3–4.5 m off the ground. Contrary to published reports, groups of Bushtits repeatedly visited fixed food sources, specifically the yellow flowers of the exotic leatherleaf mahonia (Mahonia bealei) for over 2 weeks on early winter mornings.

The neural crest is a unique population of cells that arise in the vertebrate ectoderm at the neural plate border after which they migrate extensively throughout the embryo, giving rise to a wide range of derivatives. A number of proteins involved in neural crest development have dynamic expression patterns, and it is becoming clear that ubiquitin-mediated protein degradation is partly responsible for this. Here we demonstrate a novel role for the F-box protein Cdc4/Fbxw7 in neural crest development. Two isoforms of Xenopus laevis Cdc4 were identified, and designated xCdc4alpha and xCdc4beta. These are highly conserved with vertebrate Cdc4 orthologs, and the Xenopus proteins are functionally equivalent in terms of their ability to degrade Cyclin E, an established vertebrate Cdc4 target. Blocking xCdc4 function specifically inhibited neural crest development at an early stage, prior to expression of c-Myc, Snail2 and Snail. We demonstrate that Cdc4, an ubiquitin E3 ligase subunit previously identified as targeting primarily cell cycle regulators for proteolysis, has additional roles in control of formation of the neural crest. Hence, we identify Cdc4 as a protein with separable but complementary functions in control of cell proliferation and differentiation.

The behavior of breast epithelial cells is influenced by their microenvironment which includes stromal cells and extracellular matrix (ECM). During cancer progression, the tissue microenvironment fails to control proliferation and differentiation, resulting in uncontrolled growth and invasion. Upon invasion, the ECM encountered by breast cancer cells changes from primarily laminin and collagen IV to primarily collagen I. We show here that culturing invasive breast cancer cells in 3-dimensional (3D) collagen I inhibits proliferation through direct regulation of cyclin E1, a G 1 /S regulator that is overexpressed in breast cancer. When the breast cancer cell line MDA-MB-231 was cultured within 3D collagen I gels, the G 1 /S transition was inhibited as compared to cells cultured on conventional 2D collagen or plastic dishes. Cells in 3D collagen downregulated cyclin E1 protein and mRNA, with no change in cyclin D1 level. Cyclin D1 was primarily cytoplasmic in 3D cultures, and this was accompanied by decreased phosphorylation of Rb, a nuclear target for both cyclin E1- and cyclin D1-associated kinases. Positive regulators of cyclin E1 expression, the transcription factor c-Myc and cold-inducible RNA binding protein (CIRP), were decreased in 3D collagen cultures, while the collagen I receptor β1 integrin was greatly increased. Inhibition of β1 integrin function rescued proliferation and cyclin E1 expression as well as c-Myc expression and Rb phosphorylation, but cyclin D1 remained cytoplasmic. We conclude that cyclin E1 is repressed independent of effects on cyclin D1 in a 3D collagen environment and dependent on β1 integrin interaction with collagen I, reducing proliferation of invasive breast cancer cells.

Luminescent semiconductor nanocrystals, also known as quantum dots (QD), possess highly desirable optical properties that account for development of a variety of exciting biomedical techniques. These properties include long-term stability, brightness, narrow emission spectra, size tunable properties and resistance to photobleaching. QD have many promising applications in biology and the list is constantly growing. These applications include DNA or protein tagging for in vitro assays, deep-tissue imaging, fluorescence resonance energy transfer (FRET), and studying dynamics of cell surface receptors, among others. Here we explored the potential of QD-mediated labeling for the purpose of tracking an intracellular protein inside live cells. We manufactured dihydrolipoic acid (DHLA)-capped CdSe-ZnS core-shell QD, not available commercially, and coupled them to the cell cycle regulatory protein Cyclin E. We then utilized the QD fluorescence capabilities for visualization of Cyclin E trafficking within cells of Xenopus laevis embryos in real time. These studies provide \"proof-of-concept\" for this approach by tracking QD-tagged Cyclin E within cells of developing embryos, before and during an important developmental period, the midblastula transition. Importantly, we show that the attachment of QD to Cyclin E did not disrupt its proper intracellular distribution prior to and during the midblastula transition. The fate of the QD after cyclin E degradation following the midblastula transition remains unknown.

Objective. To determine whether second-born twins (B) have higher morbidity and mortality than first-born twins (A), using a paired analysis. Study design. We conducted a retrospective analysis of birth certificates and fetal and infant death certificates for 5138 twin pairs selected from those born in Washington State from 1989 to 2001. Twin A was vertex and delivered vaginally. Pairs were not size-discordant ( < 20%) and had no malformations. Matched-pair odds ratios were calculated. Results. Twin B had more fetal distress (OR = 6.0) and more low 5-min Apgar scores (OR = 2.1) than Twin A, except at short delivery intervals. Pairs had relatively high rates of combined vaginal plus cesarean deliveries at delivery intervals 15 min. Conclusion. If prompt vaginal delivery of Twin B does not occur, the benefits of vaginal delivery for Twin A might not outweigh the risks of distress and low Apgar scores in Twin B and vaginal plus cesarean delivery for the mother.

We recorded Bushtit (Psaltriparus minimus) flock size on the Seattle University campus across multiple seasons in order to characterize the timing of pair formation prior to nest building in Washington state and compare it to that of California and Arizona. We also collected autumn and winter foraging locations, specifically vegetation types and foraging heights. We found the disbanding of large flocks (15-20 birds) into nest-building pairs occurred 1-2 months later in the northern part of the Bushtit's range than what is reported in more southern states. Bushtits spent a similar percentage of time foraging in deciduous trees, evergreen trees, and mixed shmbs in fall and winter, often moving along garden strips at heights of 3-4.5 m off the ground. Contrary to published reports, groups of Bushtits repeatedly visited fixed food sources, specifically the yellow flowers of the exotic leatherleaf mahonia (Mahonia bealei) for over 2 weeks on early winter mornings. Received 22 August 2019. Accepted I October 2021.

We recorded Bushtit (Psaltriparus minimus) flock size on the Seattle University campus across multiple seasons in order to characterize the timing of pair formation prior to nest building in Washington state and compare it to that of California and Arizona. We also collected autumn and winter foraging locations, specifically vegetation types and foraging heights. We found the disbanding of large flocks (15-20 birds) into nest-building pairs occurred 1-2 months later in the northern part of the Bushtit's range than what is reported in more southern states. Bushtits spent a similar percentage of time foraging in deciduous trees, evergreen trees, and mixed shmbs in fall and winter, often moving along garden strips at heights of 3-4.5 m off the ground. Contrary to published reports, groups of Bushtits repeatedly visited fixed food sources, specifically the yellow flowers of the exotic leatherleaf mahonia (Mahonia bealei) for over 2 weeks on early winter mornings. Received 22 August 2019. Accepted I October 2021.

The behavior of breast epithelial cells is influenced by their microenvironment which includes stromal cells and extracellular matrix (ECM). During cancer progression, the tissue microenvironment fails to control proliferation and differentiation, resulting in uncontrolled growth and invasion. Upon invasion, the ECM encountered by breast cancer cells changes from primarily laminin and collagen IV to primarily collagen I. We show here that culturing invasive breast cancer cells in 3-dimensional (3D) collagen I inhibits proliferation through direct regulation of cyclin E1, a [G.sub.1]/S regulator that is overexpressed in breast cancer. When the breast cancer cell line MDAMB-231 was cultured within 3D collagen I gels, the [G.sub.1]/S transition was inhibited as compared to cells cultured on conventional 2D collagen or plastic dishes. Cells in 3D collagen downregulated cyclin E1 protein and mRNA, with no change in cyclin D1 level. Cyclin D1 was primarily cytoplasmic in 3D cultures, and this was accompanied by decreased phosphorylation of Rb, a nuclear target for both cyclin E1- and cyclin D1-associated kinases. Positive regulators of cyclin E1 expression, the transcription factor c-Myc and cold-inducible RNA binding protein (CIRP), were decreased in 3D collagen cultures, while the collagen I receptor [beta]1 integrin was greatly increased. Inhibition of [beta]1 integrin function rescued proliferation and cyclin E1 expression as well as c-Myc expression and Rb phosphorylation, but cyclin D1 remained cytoplasmic. We conclude that cyclin E1 is repressed independent of effects on cyclin D1 in a 3D collagen environment and dependent on [beta]1 integrin interaction with collagen I, reducing proliferation of invasive breast cancer cells. Keywords 3-Dimensional collagen, Breast cancer, Cyclin E1, Cell cycle, [beta]1 Integrin