Microbiota-Derived Natural Products Targeting Cancer Stem Cells: Inside the Gut Pharma Factory

Cancer stem cells (CSCs) have drawn much attention as important tumour-initiating cells that may also be crucial for recurrence after chemotherapy. Although the activity of CSCs in various forms of cancer is complex and yet to be fully elucidated, opportunities for therapies targeting CSCs exist. CSCs are molecularly distinct from bulk tumour cells, so they can be targeted by exploiting their signature molecular pathways. Inhibiting stemness has the potential to reduce the risk posed by CSCs by limiting or eliminating their capacity for tumorigenesis, proliferation, metastasis, and recurrence. Here, we briefly described the role of CSCs in tumour biology, the mechanisms involved in CSC therapy resistance, and the role of the gut microbiota in cancer development and treatment, to then review and discuss the current advances in the discovery of microbiota-derived natural compounds targeting CSCs. Collectively, our overview suggests that dietary intervention, toward the production of those identified microbial metabolites capable of suppressing CSC properties, is a promising approach to support standard chemotherapy

Green and Roasted Coffee Extracts Inhibit Interferon-β Release in LPS-Stimulated Human Macrophages

The anti-inflammatory activity of coffee extracts is widely recognized and supported by experimental evidence, in both in vitro and in vivo settings, mainly murine models. Here, we investigated the immunomodulatory properties of coffee extracts from green (GCE) and medium-roasted (RCE) Coffea canephora beans in human macrophages. The biological effect of GCE and RCE was characterized in LPS-stimulated THP-1-derived human macrophages (TDM) as a model of inflammation. Results showed decreased amounts of TNF-α, IL-6 and IL-1β and a strong dose-dependent inhibition of interferon-β (IFN-β) release. Molecular mechanism of IFN-β inhibition was further investigated by immunofluorescence confocal microscopy analysis that showed a diminished nuclear translocation of p-IRF-3, the main transcription factor responsible for IFN-β synthesis. The inhibition of IFN-β release by RCE and GCE was also confirmed in human primary CD14+ monocytes-derived macrophages (MDM). The main component of coffee extracts, 5-O-caffeoylquinic acid (5-CQA) also inhibited IFN-β production, through a mechanism occurring downstream to TLR4. Inhibition of IFN-β release by coffee extracts parallels with the activity of their main phytochemical component, 5-CQA, thus suggesting that this compound is the main responsible for the immunomodulatory effect observed. The application of 5-CQA and coffee derived-phytoextracts to target interferonopathies and inflammation-related diseases could open new pharmacological and nutritional perspectives

Mapping the CMB Sky: The BOOMERANG experiment

We describe the BOOMERanG experiment, a stratospheric balloon telescope intended to measure the Cosmic Microwave Background anisotropy at angular scales between a few degrees and ten arcminutes. The experiment has been optimized for a long duration (7 to 14 days) flight circumnavigating Antarctica at the end of 1998. A test flight was performed on Aug.30, 1997 in Texas. The level of performance achieved in the test flight was satisfactory and compatible with the requirements for the long duration flight.Comment: 11 pages, 6 figure

First array of enriched Zn82^{82}Se bolometers to search for double beta decay

The R&D activity performed during the last years proved the potential of ZnSe scintillating bolometers to the search for neutrino-less double beta decay, motivating the realization of the first large-mass experiment based on this technology: CUPID-0. The isotopic enrichment in $^{82}$Se, the Zn$^{82}$Se crystals growth, as well as the light detectors production have been accomplished, and the experiment is now in construction at Laboratori Nazionali del Gran Sasso (Italy). In this paper we present the results obtained testing the first three Zn$^{82}$Se crystals operated as scintillating bolometers, and we prove that their performance in terms of energy resolution, background rejection capability and intrinsic radio-purity complies with the requirements of CUPID-0

BOOMERanG: a scanning telescope for 10 arcminutes resolution CMB maps

The BOOMERanG experiment is a stratospheric balloon telescope intended to measure the Cosmic Microwave Background anisotropy at angular scales between a few degrees and ten arcminutes. The experiment features a wide focal plane with 16 detectors in the frequency bands centered at 90, 150, 220, 400 GHz, with FWHM ranging between 18 and 10 arcmin. It will be flown on a long duration (7-14 days) flight circumnavigating Antarctica at the end of 1998. The instrument was flown with a reduced focal plane (6 detectors, 90 and 150 GHz bands, 25 to 15 arcmin FWHM) on a qualification flight from Texas, in August 1997. A wide (~300 sq. deg, i.e. about 5000 independent beams at 150 GHz) sky area was mapped in the constellations of Capricornus, Aquarius, Cetus, with very low foreground contamination. The instrument was calibrated using the CMB dipole and observations of Jupiter. The LDB version of the instrument has been qualified and shipped to Antarctica

CUORE and beyond: bolometric techniques to explore inverted neutrino mass hierarchy

The CUORE (Cryogenic Underground Observatory for Rare Events) experiment will search for neutrinoless double beta decay of $^{130}$Te. With 741 kg of TeO$_2$ crystals and an excellent energy resolution of 5 keV (0.2%) at the region of interest, CUORE will be one of the most competitive neutrinoless double beta decay experiments on the horizon. With five years of live time, CUORE projected neutrinoless double beta decay half-life sensitivity is $1.6\times 10^{26}$ y at $1\sigma$ ($9.5\times10^{25}$ y at the 90% confidence level), which corresponds to an upper limit on the effective Majorana mass in the range 40--100 meV (50--130 meV). Further background rejection with auxiliary light detector can significantly improve the search sensitivity and competitiveness of bolometric detectors to fully explore the inverted neutrino mass hierarchy with $^{130}$Te and possibly other double beta decay candidate nuclei.Comment: Submitted to the Proceedings of TAUP 2013 Conferenc

Exploring the Neutrinoless Double Beta Decay in the Inverted Neutrino Hierarchy with Bolometric Detectors

Neutrinoless double beta decay (0nubb) is one of the most sensitive probes for physics beyond the Standard Model, providing unique information on the nature of neutrinos. In this paper we review the status and outlook for bolometric 0nubb decay searches. We summarize recent advances in background suppression demonstrated using bolometers with simultaneous readout of heat and light signals. We simulate several configurations of a future CUORE-like bolometer array which would utilize these improvements and present the sensitivity reach of a hypothetical next-generation bolometric 0nubb experiment. We demonstrate that a bolometric experiment with the isotope mass of about 1 ton is capable of reaching the sensitivity to the effective Majorana neutrino mass (|mee|) of order 10-20 meV, thus completely exploring the so-called inverted neutrino mass hierarchy region. We highlight the main challenges and identify priorities for an R&D program addressing them.Comment: 22 pages, 15 figures, submitted to EPJ

CUORE-0 results and prospects for the CUORE experiment

With 741 kg of TeO2 crystals and an excellent energy resolution of 5 keV (0.2%) at the region of interest, the CUORE (Cryogenic Underground Observatory for Rare Events) experiment aims at searching for neutrinoless double beta decay of 130Te with unprecedented sensitivity. Expected to start data taking in 2015, CUORE is currently in an advanced construction phase at LNGS. CUORE projected neutrinoless double beta decay half-life sensitivity is 1.6E26 y at 1 sigma (9.5E25 y at the 90% confidence level), in five years of live time, corresponding to an upper limit on the effective Majorana mass in the range 40-100 meV (50-130 meV). Further background rejection with auxiliary bolometric detectors could improve CUORE sensitivity and competitiveness of bolometric detectors towards a full analysis of the inverted neutrino mass hierarchy. CUORE-0 was built to test and demonstrate the performance of the upcoming CUORE experiment. It consists of a single CUORE tower (52 TeO2 bolometers of 750 g each, arranged in a 13 floor structure) constructed strictly following CUORE recipes both for materials and assembly procedures. An experiment its own, CUORE-0 is expected to reach a sensitivity to the neutrinoless double beta decay half-life of 130Te around 3E24 y in one year of live time. We present an update of the data, corresponding to an exposure of 18.1 kg y. An analysis of the background indicates that the CUORE performance goal is satisfied while the sensitivity goal is within reach.Comment: 10 pages, 3 figures, to appear in the proceedings of NEUTRINO 2014, 26th International Conference on Neutrino Physics and Astrophysics, 2-7 June 2014, held at Boston, Massachusetts, US

Validation of techniques to mitigate copper surface contamination in CUORE

In this article we describe the background challenges for the CUORE experiment posed by surface contamination of inert detector materials such as copper, and present three techniques explored to mitigate these backgrounds. Using data from a dedicated test apparatus constructed to validate and compare these techniques we demonstrate that copper surface contamination levels better than 10E-07 - 10E-08 Bq/cm2 are achieved for 238U and 232Th. If these levels are reproduced in the final CUORE apparatus the projected 90% C.L. upper limit on the number of background counts in the region of interest is 0.02-0.03 counts/keV/kg/y depending on the adopted mitigation technique.Comment: 10 pages, 6 figures, 6 table

Search for 14.4 keV solar axions from M1 transition of Fe-57 with CUORE crystals

We report the results of a search for axions from the 14.4 keV M1 transition from Fe-57 in the core of the sun using the axio-electric effect in TeO2 bolometers. The detectors are 5x5x5 cm3 crystals operated at about 10 mK in a facility used to test bolometers for the CUORE experiment at the Laboratori Nazionali del Gran Sasso in Italy. An analysis of 43.65 kg d of data was made using a newly developed low energy trigger which was optimized to reduce the detectors energy threshold. An upper limit of 0.63 c kg-1 d-1 was established at 95% C.L.. From this value, a lower bound at 95% C.L. was placed on the Peccei-Quinn energy scale of fa >= 0.76 10**6 GeV for a value of S=0.55 for the flavor-singlet axial vector matrix element. Bounds are given for the interval 0.15 < S < 0.55.Comment: 14 pages, 6 figures, submitted to JCA