GPER-induced signaling is essential for the survival of breast cancer stem cells.

G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER- /PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs

Factors Related to Intra-Tendinous Morphology of Achilles Tendon in Runners

The purpose of this study was to determine and explore factors (age, sex, anthropometry, running and injury/pain history, tendon gross morphology, neovascularization, ankle range of motion, and ankle plantarflexor muscle endurance) related to intra-tendinous morphological alterations of the Achilles tendon in runners. An intra-tendinous morphological change was defined as collagen fiber disorganization detected by a low peak spatial frequency radius (PSFR) obtained from spatial frequency analysis (SFA) techniques in sonography. Ninety-one runners (53 males and 38 females; 37.9 ± 11.6 years) with 8.8 ± 7.3 years of running experience participated. Height, weight, and waist and hip circumferences were recorded. Participants completed a survey about running and injury/pain history and the Victorian Institute of Sport Assessment-Achilles (VISA-A) survey. Heel raise endurance and knee-to-wall composite dorsiflexion were assessed. Brightness-mode (B-mode) sonographic images were captured longitudinally and transversely on the Achilles tendon bilaterally. Sonographic images were analyzed for gross morphology (i.e., cross-sectional area [CSA]), neovascularization, and intra-tendinous morphology (i.e., PSFR) for each participant. The factors associated with altered intra-tendinous morphology of the Achilles tendon were analyzed using a generalized linear mixed model. Multivariate analyses revealed that male sex was significantly associated with a decreased PSFR. Additionally, male sex and the presence of current Achilles tendon pain were found to be significantly related to decreased PSFR using a univariate analysis. Our findings suggested that male sex and presence of current Achilles tendon pain were related to intra-tendinous morphological alterations in the Achilles tendon of runners

Patellar Tendon Morphology in Trans-tibial Amputees Utilizing a Prosthesis with a Patellar-tendon- Bearing Feature

A patellar-tendon-bearing (PTB) bar is a common design feature used in the socket of trans-tibial prostheses to place load on the pressure-tolerant tissue. As the patellar tendon in the residual limb is subjected to the perpendicular compressive force not commonly experienced in normal tendons, it is possible for tendon degeneration to occur over time. The purpose of this study was to compare patellar tendon morphology and neovascularity between the residual and intact limbs in trans-tibial amputees and healthy controls. Fifteen unilateral trans-tibial amputees who utilized a prosthesis with a PTB feature and 15 age- and sex- matched controls participated. Sonography was performed at the proximal, mid-, and distal portions of each patellar tendon. One-way ANOVAs were conducted to compare thickness and collagen fber organization and a chi-square analysis was used to compare the presence of neovascularity between the three tendon groups. Compared to healthy controls, both tendons in the amputees exhibited increased thickness at the mid- and distal portions and a higher degree of collagen fber disorganization. Furthermore, neovascularity was more common in the tendon of the residual limb. Our results suggest that the use of a prosthesis with a PTB feature contributes to morphological changes in bilateral patellar tendons

5-Hy­droxy­indan-1-one

In the title compound (5HIN), C9H8O2, is perfectly planar as all atoms, except the H atoms of both CH2 groups, lie on a crystallographic mirror plane. In the crystal, mol­ecules are linked by strong inter­molecular O—H⋯O hydrogen bonds, forming an infinite chain along [100], generating a C(8) motif

Growth rate regulation of lac operon expression in Escherichia coli is cyclic AMP dependent

AbstractIn contrast to the ribosomal RNA gene expression increasing with growth rate, transcription of the lac operon is downregulated by cell growth rate. In continuous culture, growth rate regulation of lac promoter was independent of carbon substrate used and its location on the chromosome. Since the lac operon is activated by cyclic adenosine monophosphate (cAMP), which decreases with increasing cell growth rate, expression of plac-lacZ reporter fusion was analyzed in cya mutant under various growth conditions. The results demonstrated that expression of plac-lacZ in cya mutant was both lower and growth rate independent. In addition, ppGpp (guanosine tetraphosphate) was not involved in the mechanism of growth rate regulation of the lac promoter. Thus, the results of this study indicate that cAMP mediates the growth rate-dependent regulation of lac operon expression in Escherichia coli

Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells.

FUT1 and FUT2 encode alpha 1, 2-fucosyltransferases which catalyze the addition of alpha 1, 2-linked fucose to glycans. Glycan products of FUT1 and FUT2, such as Globo H and Lewis Y, are highly expressed on malignant tissues, including breast cancer. Herein, we investigated the roles of FUT1 and FUT2 in breast cancer. Silencing of FUT1 or FUT2 by shRNAs inhibited cell proliferation in vitro and tumorigenicity in mice. This was associated with diminished properties of cancer stem cell (CSC), including mammosphere formation and CSC marker both in vitro and in xenografts. Silencing of FUT2, but not FUT1, significantly changed the cuboidal morphology to dense clusters of small and round cells with reduced adhesion to polystyrene and extracellular matrix, including laminin, fibronectin and collagen. Silencing of FUT1 or FUT2 suppressed cell migration in wound healing assay, whereas FUT1 and FUT2 overexpression increased cell migration and invasion in vitro and metastasis of breast cancer in vivo. A decrease in mesenchymal like markers such as fibronectin, vimentin, and twist, along with increased epithelial like marker, E-cadherin, was observed upon FUT1/2 knockdown, while the opposite was noted by overexpression of FUT1 or FUT2. As expected, FUT1 or FUT2 knockdown reduced Globo H, whereas FUT1 or FUT2 overexpression showed contrary effects. Exogenous addition of Globo H-ceramide reversed the suppression of cell migration by FUT1 knockdown but not the inhibition of cell adhesion by FUT2 silencing, suggesting that at least part of the effects of FUT1/2 knockdown were mediated by Globo H. Our results imply that FUT1 and FUT2 play important roles in regulating growth, adhesion, migration and CSC properties of breast cancer, and may serve as therapeutic targets for breast cancer