Finger-gate manipulated quantum transport in a semiconductor narrow constriction with spin-orbit interactions and Zeeman effect

The authors investigate quantum transport in a narrow constriction fabricated by narrow band gap semiconductor materials with spin-orbit (SO) couplings. We consider the Rashba-Dresselhaus (RD) spin-orbit interactions (SOIs) and the Zeeman effect induced by an in-plane magnetic field along the transport direction. The interplay of the RD-SOI and the Zeeman effect may induce a SOI-Zeeman gap and influence the transport properties. We demonstrate that an attractive scattering potential may induce electron-like quasi-bound-state feature and manifest the RD-SOI-Zeeman induced Fano line-shape in conductance. Furthermore, a repulsive scattering potential may induce hole-like quasi-bound-state feature on the subband top of the lower spin branch.Comment: 10 pages, 9 figure

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

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

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

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

GenEpi: gene-based epistasis discovery using machine learning.

BackgroundGenome-wide association studies (GWAS) provide a powerful means to identify associations between genetic variants and phenotypes. However, GWAS techniques for detecting epistasis, the interactions between genetic variants associated with phenotypes, are still limited. We believe that developing an efficient and effective GWAS method to detect epistasis will be a key for discovering sophisticated pathogenesis, which is especially important for complex diseases such as Alzheimer's disease (AD).ResultsIn this regard, this study presents GenEpi, a computational package to uncover epistasis associated with phenotypes by the proposed machine learning approach. GenEpi identifies both within-gene and cross-gene epistasis through a two-stage modeling workflow. In both stages, GenEpi adopts two-element combinatorial encoding when producing features and constructs the prediction models by L1-regularized regression with stability selection. The simulated data showed that GenEpi outperforms other widely-used methods on detecting the ground-truth epistasis. As real data is concerned, this study uses AD as an example to reveal the capability of GenEpi in finding disease-related variants and variant interactions that show both biological meanings and predictive power.ConclusionsThe results on simulation data and AD demonstrated that GenEpi has the ability to detect the epistasis associated with phenotypes effectively and efficiently. The released package can be generalized to largely facilitate the studies of many complex diseases in the near future

Sialylation of vasorin by ST3Gal1 facilitates TGF-β1-mediated tumor angiogenesis and progression.

ST3Gal1 is a key sialyltransferase which adds α2,3-linked sialic acid to substrates and generates core 1 O-glycan structure. Upregulation of ST3Gal1 has been associated with worse prognosis of breast cancer patients. However, the protein substrates of ST3Gal1 implicated in tumor progression remain elusive. In our study, we demonstrated that ST3GAL1-silencing significantly reduced tumor growth along with a notable decrease in vascularity of MCF7 xenograft tumors. We identified vasorin (VASN) which was shown to bind TGF-β1, as a potential candidate that links ST3Gal1 to angiogenesis. LC-MS/MS analysis of VASN secreted from MCF7, revealed that more than 80% of its O-glycans are sialyl-3T and disialyl-T. ST3GAL1-silencing or desialylation of VASN by neuraminidase enhanced its binding to TGF-β1 by 2- to 3-fold and thereby dampening TGF-β1 signaling and angiogenesis, as indicated by impaired tube formation of HUVECs, suppressed angiogenesis gene expression and reduced activation of Smad2 and Smad3 in HUVEC cells. Examination of 114 fresh primary breast cancer and their adjacent normal tissues showed that the expression levels of ST3Gal1 and TGFB1 were high in tumor part and the expression of two genes was positively correlated. Kaplan Meier survival analysis showed a significantly shorter relapse-free survival for those with lower expression VASN, notably, the combination of low VASN with high ST3GAL1 yielded even higher risk of recurrence (p = 0.025, HR = 2.967, 95% CI = 1.14-7.67). Since TGF-β1 is known to transcriptionally activate ST3Gal1, our findings illustrated a feedback regulatory loop in which TGF-β1 upregulates ST3Gal1 to circumvent the negative impact of VASN