Detection of circulating carcinoma cells by telomerase activity

Telomerase has been shown to be a marker of epithelial cancer cells. We developed a method that allows the detection of circulating carcinoma cells in the blood of cancer patients. Circulating epithelial cells are harvested from peripheral blood mononuclear cells by immunomagnetic separation using BerEP4-coated beads. A telomeric repeat amplification protocol (TRAP)-ELISA is then used to measure telomerase in harvested epithelial cells. This method is specific and sensitive as demonstrated by experiments using BerEP4-positive and negative cell lines. Whereas we never found telomerase activity in harvested epithelial cells (HEC) samples from 30/30 healthy donors, we have detected telomerase activity in HEC from 11/15 (73%) patients with stage IIIB or IV non-small cell lung cancer (NSCLC) patients and from 8/11 (72%) stage C or D (Dukes classification) colon cancer patients. This non-invasive method could be of great value as a diagnostic or prognostic marker, or for monitoring cancer progression. © 2001 Cancer Research Campaign http://www.bjcancer.co

Comprehensive analysis of a symbiotic candidate V503 Her

V503 Her was previously proposed as an eclipsing symbiotic candidate based on photometric behavior and spectroscopic appearance indicating the composite optical spectrum. To investigate its nature, we analyzed long-term photometric observations covering one hundred years of its photometric history and new low-resolution optical spectroscopic data, supplemented with the multifrequency measurements collected from several surveys and satellites. Based on the analysis presented in this paper, we claim that V503 Her is not an eclipsing binary star. The optical and infrared wavelengths are dominated by a K-type bright giant with an effective temperature of 4 500 K, luminosity of 1 900 L$_\odot$, and sub-solar metallicity on the asymptotic giant branch showing semiregular complex multi-periodic pulsation behavior. V503 Her does not show the characteristics of strongly interacting symbiotic variables, but some pieces of evidence suggest that it could still be one of the 'hidden' accreting-only symbiotic systems. However, the currently available data do not allow us to fully confirm or constrain the parameters of a possible companion.Comment: 16 pages, 10 figures, 4 tables; accepted in the Astronomical Journa

Impact of the hypoxic microenvironment on spermatogonial stem cells in culture

The stem cell niche plays a crucial role in the decision to either self-renew or differentiate. Recent observations lead to the hypothesis that O2 supply by blood and local O2 tension could be key components of the testicular niche of spermatogonial stem cells (SSCs). In this study, we investigated the impact of different hypoxic conditions (3.5%, 1%, and 0.1% O2 tension) on murine and human SSCs in culture. We observed a deleterious effect of severe hypoxia (1% O2 and 0.1% O2) on the capacity of murine SSCs to form germ cell clusters when plated at low density. Severe effects on SSCs proliferation occur at an O2 tension ≤1% and hypoxia was shown to induce a slight differentiation bias under 1% and 0.1% O2 conditions. Exposure to hypoxia did not appear to change the mitochondrial mass and the potential of membrane of mitochondria in SSCs, but induced the generation of mitochondrial ROS at 3.5% and 1% O2. In 3.5% O2 conditions, the capacity of SSCs to form colonies was maintained at the level of 21% O2 at low cell density, but it was impossible to amplify and maintain stem cell number in high cell density culture. In addition, we observed that 3.5% hypoxia did not improve the maintenance and propagation of human SSCs. Finally, our data tend to show that the transcription factors HIF-1α and HIF-2α are not involved in the SSCs cell autonomous response to hypoxia

Rad51 and DNA-PKcs are involved in the generation of specific telomere aberrations induced by the quadruplex ligand 360A that impair mitotic cell progression and lead to cell death

Functional telomeres are protected from non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways. Replication is a critical period for telomeres because of the requirement for reconstitution of functional protected telomere conformations, a process that involves DNA repair proteins. Using knockdown of DNA-PKcs and Rad51 expression in three different cell lines, we demonstrate the respective involvement of NHEJ and HR in the formation of telomere aberrations induced by the G-quadruplex ligand 360A during or after replication. HR contributed to specific chromatid-type aberrations (telomere losses and doublets) affecting the lagging strand telomeres, whereas DNA-PKcs-dependent NHEJ was responsible for sister telomere fusions as a direct consequence of G-quadruplex formation and/or stabilization induced by 360A on parental telomere G strands. NHEJ and HR activation at telomeres altered mitotic progression in treated cells. In particular, NHEJ-mediated sister telomere fusions were associated with altered metaphase-anaphase transition and anaphase bridges and resulted in cell death during mitosis or early G1. Collectively, these data elucidate specific molecular and cellular mechanisms triggered by telomere targeting by the G-quadruplex ligand 360A, leading to cancer cell death

V392 Persei: a γ-ray bright nova eruption from a known dwarf nova

V392 Persei is a known dwarf nova (DN) that underwent a classical nova eruption in 2018. Here we report ground-based optical, Swift UV and X-ray, and Fermi-LAT γ-ray observations following the eruption for almost three years. V392 Per is one of the fastest evolving novae yet observed, with a t2 decline time of 2 days. Early spectra present evidence for multiple and interacting mass ejections, with the associated shocks driving both the γ-ray and early optical luminosity. V392 Per entered Sun-constraint within days of eruption. Upon exit, the nova had evolved to the nebular phase, and we saw the tail of the super-soft X-ray phase. Subsequent optical emission captured the fading ejecta alongside a persistent narrow line emission spectrum from the accretion disk. Ongoing hard X-ray emission is characteristic of a standing accretion shock in an intermediate polar. Analysis of the optical data reveals an orbital period of 3.230 ± 0.003 days, but we see no evidence for a white dwarf (WD) spin period. The optical and X-ray data suggest a high mass WD, the pre-nova spectral energy distribution (SED) indicates an evolved donor, and the post-nova SED points to a high mass accretion rate. Following eruption, the system has remained in a nova-like high mass transfer state, rather than returning to the pre-nova DN low mass transfer configuration. We suggest that this high state is driven by irradiation of the donor by the nova eruption. In many ways, V392 Per shows similarity to the well-studied nova and DN GK Persei

MRI characterization of long-term brain damage induced by low dose

CERVOXYInternational audienc

Characterization of long-term cerebral alterations in a mouse model of in utero high dose irradiation using anatomical and diffusion MRI

CERVOXY COLLInternational audienc