14 research outputs found
The non-Abelian geometric phase in the diamond nitrogen-vacancy center
This paper introduces a theoretical framework for understanding the
accumulation of non-Abelian geometric phases in rotating nitrogen-vacancy
centers in diamond. Specifically, we consider how degenerate states can be
achieved and demonstrate that the resulting geometric phase for multiple paths
is non-Abelian. We find that the non-Abelian nature of the phase is robust to
fluctuations in the path and magnetic field. In contrast to previous studies of
the accumulation of Abelian geometric phases for nitrogen-vacancy centers under
rotation we find that the limiting time-scale is . As such a non-Abelian
geometric phase accumulation in nitrogen-vacancy centers has potential
advantages for applications as gyroscopes.Comment: 5 pages, including 4 figure
CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy.
Ovarian cancer and triple-negative breast cancer are among the most lethal diseases affecting women, with few targeted therapies and high rates of metastasis. Cancer cells are capable of evading clearance by macrophages through the overexpression of anti-phagocytic surface proteins called 'don't eat me' signals-including CD471, programmed cell death ligand 1 (PD-L1)2 and the beta-2 microglobulin subunit of the major histocompatibility class I complex (B2M)3. Monoclonal antibodies that antagonize the interaction of 'don't eat me' signals with their macrophage-expressed receptors have demonstrated therapeutic potential in several cancers4,5. However, variability in the magnitude and durability of the response to these agents has suggested the presence of additional, as yet unknown 'don't eat me' signals. Here we show that CD24 can be the dominant innate immune checkpoint in ovarian cancer and breast cancer, and is a promising target for cancer immunotherapy. We demonstrate a role for tumour-expressed CD24 in promoting immune evasion through its interaction with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which is expressed by tumour-associated macrophages. We find that many tumours overexpress CD24 and that tumour-associated macrophages express high levels of Siglec-10. Genetic ablation of either CD24 or Siglec-10, as well as blockade of the CD24-Siglec-10 interaction using monoclonal antibodies, robustly augment the phagocytosis of all CD24-expressing human tumours that we tested. Genetic ablation and therapeutic blockade of CD24 resulted in a macrophage-dependent reduction of tumour growth in vivo and an increase in survival time. These data reveal CD24 as a highly expressed, anti-phagocytic signal in several cancers and demonstrate the therapeutic potential for CD24 blockade in cancer immunotherapy
Devil Facial Tumor Disease, A Potential Model of the Cancer Stem-Cell Process?
Tasmanian devil facial tumor disease (DFTD) is a naturally occurring contagious cancer which is transmitted as a clonal cell line between devils. The malignant cell line evolved from a Schwann cell or precursor prior to 1996 and since then has undergone continuous division without exhausting its replicative potential, suggesting a profound capacity for self renewal. It is therefore important to elucidate whether DFTD may have a stem cell origin. Deciphering the pathways regulating DFT cell proliferation and survival could lead to increased understanding of this transimissible cancer and to the development of successful therapies to halt the disease. We investigated whether DFT cells have originated from transformed stem cells by measuring the expression levels of thirteen genes characteristic to embryonic stem and/or pluripotent germ cells. No differences in gene expression were observed between DFT cells and peripheral nerve controls, and therefore our results provide additional support for Schwann cell or peripheral nerve origin of DFTD. Although our dataset is preliminary, it does not suggest that DFTs have cancer stem cells (CSCs) origin. We provide details of further experiments needed to ultimately confirm the role of cancer stem cells in DFTD progression
Tracking individual nanodiamonds in Drosophila melanogaster embryos
Tracking the dynamics of fluorescent nanoparticles during embryonic
development allows insights into the physical state of the embryo and,
potentially, molecular processes governing developmental mechanisms. In this
work, we investigate the motion of individual fluorescent nanodiamonds
micro-injected into Drosophila melanogaster embryos prior to cellularisation.
Fluorescence correlation spectroscopy and wide-field imaging techniques are
applied to individual fluorescent nanodiamonds in blastoderm cells during stage
5 of development to a depth of ~40 \mu m. The majority of nanodiamonds in the
blastoderm cells during cellularisation exhibit free diffusion with an average
diffusion coefficient of (6 3) x 10 \mu m/s, (mean SD).
Driven motion in the blastoderm cells was also observed with an average
velocity of 0.13 0.10 \mu m/s (mean SD) \mu m/s and an average
applied force of 0.07 0.05 pN (mean SD). Nanodiamonds in the
periplasm between the nuclei and yolk were also found to undergo free diffusion
with a significantly larger diffusion coefficient of (63 35) x10
\mu m/s (mean SD). Driven motion in this region exhibited similar
average velocities and applied forces compared to the blastoderm cells
indicating the transport dynamics in the two cytoplasmic regions are analogous.Comment: 20 pages, 6 figure
Stemness Activity Underlying Whole Brain Regeneration in a Basal Chordate
Understanding how neurons regenerate following injury remains a central challenge in regenerative medicine. Adult mammals have a very limited ability to regenerate new neurons in the central nervous system (CNS). In contrast, the basal chordate Polycarpa mytiligera can regenerate its entire CNS within seven days of complete removal. Transcriptome sequencing, cellular labeling, and proliferation in vivo essays revealed that CNS regeneration is mediated by a newly formed neural progeny and the activation of neurodevelopmental pathways that are associated with enhanced stem-cell activity. Analyzing the expression of 239 activated pathways enabled a quantitative understanding of gene-set enrichment patterns at key regeneration stages. The molecular and cellular mechanisms controlling the regenerative ability that this study reveals can be used to develop innovative approaches to enhancing neurogenesis in closely-related chordate species, including humans
Recommended from our members
CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy.
Ovarian cancer and triple-negative breast cancer are among the most lethal diseases affecting women, with few targeted therapies and high rates of metastasis. Cancer cells are capable of evading clearance by macrophages through the overexpression of anti-phagocytic surface proteins called 'don't eat me' signals-including CD471, programmed cell death ligand 1 (PD-L1)2 and the beta-2 microglobulin subunit of the major histocompatibility class I complex (B2M)3. Monoclonal antibodies that antagonize the interaction of 'don't eat me' signals with their macrophage-expressed receptors have demonstrated therapeutic potential in several cancers4,5. However, variability in the magnitude and durability of the response to these agents has suggested the presence of additional, as yet unknown 'don't eat me' signals. Here we show that CD24 can be the dominant innate immune checkpoint in ovarian cancer and breast cancer, and is a promising target for cancer immunotherapy. We demonstrate a role for tumour-expressed CD24 in promoting immune evasion through its interaction with the inhibitory receptor sialic-acid-binding Ig-like lectin 10 (Siglec-10), which is expressed by tumour-associated macrophages. We find that many tumours overexpress CD24 and that tumour-associated macrophages express high levels of Siglec-10. Genetic ablation of either CD24 or Siglec-10, as well as blockade of the CD24-Siglec-10 interaction using monoclonal antibodies, robustly augment the phagocytosis of all CD24-expressing human tumours that we tested. Genetic ablation and therapeutic blockade of CD24 resulted in a macrophage-dependent reduction of tumour growth in vivo and an increase in survival time. These data reveal CD24 as a highly expressed, anti-phagocytic signal in several cancers and demonstrate the therapeutic potential for CD24 blockade in cancer immunotherapy
Single-Cell RNA-Seq Analysis of Infiltrating Neoplastic Cells at the Migrating Front of Human Glioblastoma
Summary: Glioblastoma (GBM) is the most common primary brain cancer in adults and is notoriously difficult to treat because of its diffuse nature. We performed single-cell RNA sequencing (RNA-seq) on 3,589 cells in a cohort of four patients. We obtained cells from the tumor core as well as surrounding peripheral tissue. Our analysis revealed cellular variation in the tumor’s genome and transcriptome. We were also able to identify infiltrating neoplastic cells in regions peripheral to the core lesions. Despite the existence of significant heterogeneity among neoplastic cells, we found that infiltrating GBM cells share a consistent gene signature between patients, suggesting a common mechanism of infiltration. Additionally, in investigating the immunological response to the tumors, we found transcriptionally distinct myeloid cell populations residing in the tumor core and the surrounding peritumoral space. Our data provide a detailed dissection of GBM cell types, revealing an abundance of information about tumor formation and migration. : Darmanis et al. perform single-cell transcriptomic analyses of neoplastic and stromal cells within and proximal to primary glioblastomas. The authors describe a population of neoplastic-infiltrating glioblastoma cells as well as a putative role of tumor-infiltrating immune cells in supporting tumor growth. Keywords: single cell, RNA-seq, glioma, glioblastoma, GBM, brain, heterogeneity, infiltrating, diffuse, checkpoin