Adoptive Transfer of Myeloid-Derived Suppressor Cells and T Cells in a Prostate Cancer Model

The adoptive transfer of immune cells for cancer, chronic infection, and autoimmunity is an emerging field that has shown promise in recent trials. The transgenic adenocarcinoma mouse prostate (TRAMP) is a classical mouse model of prostate cancer (PCa) and TRAMP cell lines were derived from a TRAMP mouse tumor. TRAMP-C2 is tumorigenic when subcutaneously (s.c.) grafted into syngeneic C57BL/6 host mice (Foster et al., 1997). This protocol will describe the adoptive transfer of purified CD11b(+)Gr1(+) double positive (DP) myeloid-derived suppressor cells (MDSC) and CD3(+) T cells in the TRAMP-C2 prostate cancer mouse model in order to establish the intrinsic functionality of these immune cells and to determine their role in tumorigenesis in vivo (Yan et al., 2014)

Dynamic acoustic field activated cell separation (DAFACS)

Advances in diagnostics, cell and stem cell technologies drive the development of application-specific tools for cell and particle separation. Acoustic micro-particle separation offers a promising avenue for highthroughput, label-free, high recovery, cell and particle separation and isolation in regenerative medicine. Here, we demonstrate a novel approach utilizing a dynamic acoustic field that is capable of separating an arbitrary size range of cells. We first demonstrate the method for the separation of particles with different diameters between 6 and 45 μm and secondly particles of different densities in a heterogeneous medium. The dynamic acoustic field is then used to separate dorsal root ganglion cells. The shearless, label-free and low damage characteristics make this method of manipulation particularly suited for biological applications. Advantages of using a dynamic acoustic field for the separation of cells include its inherent safety and biocompatibility, the possibility to operate over large distances (centimetres), high purity (ratio of particle population, up to 100%), and high efficiency (ratio of separated particles over total number of particles to separate, up to 100%)

Fellowship, Service, and the \u27Spirit of Adventure\u27: The Religious Society of Friends and the Outdoors Movement in Britain, C. 1900-1950

This article considers the involvement of members of the Religious Society of Friends in various manifestations of the outdoors movement in early twentieth-century Britain. It examines the Edwardian \u27Quaker tramps\u27 and their role in the \u27Quaker renaissance\u27, and goes on to consider the influence of Friends in organisations such as the Holiday Fellowship and the Youth Hostels Association, as well as interwar Quaker mountaineers. It argues that, while the outdoor activities of the Quaker renaissance were essentially internal to the Religious Society of Friends, a wider conception of social service took Quakers beyond the boundaries of the Society in the interwar period, resulting in a more profound influence on the outdoors movement. These activities of Friends were associated with the promotion of the \u27social gospel\u27, and represented a significant strand of Quaker service in the first half of the twentieth century

RNA Unwinding by the Trf4/Air2/Mtr4 Polyadenylation (TRAMP) Complex

Many RNA-processing events in the cell nucleus involve the Trf4/Air2/Mtr4 polyadenylation (TRAMP) complex, which contains the poly(A) polymerase Trf4p, the Zn-knuckle protein Air2p, and the RNA helicase Mtr4p. TRAMP polyadenylates RNAs designated for processing by the nuclear exosome. In addition, TRAMP functions as an exosome cofactor during RNA degradation, and it has been speculated that this role involves disruption of RNA secondary structure. However, it is unknown whether TRAMP displays RNA unwinding activity. It is also not clear how unwinding would be coordinated with polyadenylation and the function of the RNA helicase Mtr4p in modulating poly(A) addition. Here, we show that TRAMP robustly unwinds RNA duplexes. The unwinding activity of Mtr4p is significantly stimulated by Trf4p/Air2p, but the stimulation of Mtr4p does not depend on ongoing polyadenylation. Nonetheless, polyadenylation enables TRAMP to unwind RNA substrates that it otherwise cannot separate. Moreover, TRAMP displays optimal unwinding activity on substrates with a minimal Mtr4p binding site comprised of adenylates. Our results suggest a model for coordination between unwinding and polyadenylation activities by TRAMP that reveals remarkable synergy between helicase and poly(A) polymerase

Exosome-mediated Transfer of αvβ3 Integrin from Tumorigenic to Nontumorigenic Cells Promotes a Migratory Phenotype.

The αvβ3 integrin is known to be highly upregulated during cancer progression and promotes a migratory and metastatic phenotype in many types of tumors. We hypothesized that the αvβ3 integrin is transferred through exosomes and, upon transfer, has the ability to support functional aberrations in recipient cells. Here, for the first time, it is demonstrated that αvβ3 is present in exosomes released from metastatic PC3 and CWR22Pc prostate cancer cells. Exosomal β3 is transferred as a protein from donor to nontumorigenic and tumorigenic cells as β3 protein or mRNA levels remain unaffected upon transcription or translation inhibition in recipient cells. Furthermore, it is shown that upon exosome uptake, de novo expression of an αvβ3 increases adhesion and migration of recipient cells on an αvβ3 ligand, vitronectin. To evaluate the relevance of these findings, exosomes were purified from the blood of TRAMP mice carrying tumors where the expression of αvβ3 is found higher than in exosomes from wild-type mice. In addition, it is demonstrated that αvβ3 is coexpressed with synaptophysin, a biomarker for aggressive neuroendocrine prostate cancer. IMPLICATIONS: Overall this study reveals that the αvβ3 integrin is transferred from tumorigenic to nontumorigenic cells via exosomes, and its de novo expression in recipient cells promotes cell migration on its ligand. The increased expression of αvβ3 in exosomes from mice bearing tumors points to its clinical relevance and potential use as a biomarker. Mol Cancer Res; 14(11); 1136-46. ©2016 AACR

Talin1 Promotes Prostate Cancer Invasion and Metastasis via AKT Signaling and Anoikis Resistance

Talin1 is an integrin regulatory protein that mediates integrin interactions with the extracellular matrix (ECM). This study investigated the significance of talin1 in prostate cancer progression to metastasis in vitro and in vivo. Talin1 overexpression enhanced prostate cancer cell adhesion, migration and invasion by activating survival signals and anoikis resistance. ShRNA-mediated talin1 loss led to a significant suppression of prostate cancer cell migration and transendothelial invasion in vitro and a significant inhibition of prostate cancer metastasis in vivo. Talin1 regulates cell survival signals via phosphorylation of focal adhesion kinase (FAK) and AKT. Targeting AKT activation led to a significant reduction of talin1-mediated prostate cancer cell invasion. Furthermore, talin1 expression was determined by immunostaining in prostate tissue from the TRAMP mouse model and in human prostate cancer specimens. Talin1 levels directly correlated with prostate tumor progression to metastasis in TRAMP mice. Talin1 profiling in human prostate specimens revealed a significantly higher expression of cytoplasmic talin1 in metastatic tissue compared to primary prostate tumors and benign prostate tissue (P<0.0001). This evidence suggests a potential value for talin1 as a marker of prostate cancer metastasis and implies that disrupting talin1 mediated signaling may have therapeutic significance in the treatment of metastatic disease

Simulating dynamical quantum Hall effect with superconducting qubits

We propose an experimental scheme to simulate the dynamical quantum Hall effect and the related interaction-induced topological transition with a superconducting-qubit array. We show that a one-dimensional Heisenberg model with tunable parameters can be realized in an array of superconducting qubits. The quantized plateaus, which is a feature of the dynamical quantum Hall effect, will emerge in the Berry curvature of the superconducting qubits as a function of the coupling strength between nearest neighbor qubits. We numerically calculate the Berry curvatures of two-, four- and six-qubit arrays, and find that the interaction-induced topological transition can be easily observed with the simplest two-qubit array. Furthermore, we analyze some practical conditions in typical experiments for observing such dynamical quantum Hall effect.Comment: 9 pages, 6 figures, version accepted by PR

Particle pair creation by inflation of quantum vacuum fluctuations in an ion trap

The creation of matter and structure in our universe is currently described by an intricate interplay of quantum field theory and general relativity. Signatures of this process during an early inflationary period can be observed, while direct tests remain out of reach. Here, we study an experimental analog of the process based on trapped atomic ions. We create pairs of phonons by tearing apart quantum vacuum fluctuations. Thereby, we prepare ions in an entangled state of motion. Controlling timescales and the coupling to environments should permit optimizing efficiencies while keeping the effect robust via established tools in quantum information processing (QIP). This might also permit to cross-fertilize between concepts in cosmology and applications of QIP, such as, quantum metrology, experimental quantum simulations and quantum computing.Comment: 35 pages, 8 figure