SPARC is a new myeloid-derived suppressor cell marker licensing suppressive activities

Myeloid-derived suppressor cells (MDSC) are well-known key negative regulators of the immune response during tumor growth, however scattered is the knowledge of their capacity to influence and adapt to the different tumor microenvironments and of the markers that identify those capacities. Here we show that the secreted protein acidic and rich in cysteine (SPARC) identifies in both human and mouse MDSC with immune suppressive capacity and pro-tumoral activities including the induction of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In mice the genetic deletion of SPARC reduced MDSC immune suppression and reverted EMT. Sparc−/− MDSC were less suppressive overall and the granulocytic fraction was more prone to extrude neutrophil extracellular traps (NET). Surprisingly, arginase-I and NOS2, whose expression can be controlled by STAT3, were not down-regulated in Sparc−/− MDSC, although less suppressive than wild type (WT) counterpart. Flow cytometry analysis showed equal phosphorylation of STAT3 but reduced ROS production that was associated with reduced nuclear translocation of the NF-kB p50 subunit in Sparc−/− than WT MDSC. The limited p50 in nuclei reduce the formation of the immunosuppressive p50:p50 homodimers in favor of the p65:p50 inflammatory heterodimers. Supporting this hypothesis, the production of TNF by Sparc−/− MDSC was significantly higher than by WT MDSC. Although associated with tumor-induced chronic inflammation, TNF, if produced at high doses, becomes a key factor in mediating tumor rejection. Therefore, it is foreseeable that an unbalance in TNF production could skew MDSC toward an inflammatory, anti-tumor phenotype. Notably, TNF is also required for inflammation-driven NETosis. The high level of TNF in Sparc−/− MDSC might explain their increased spontaneous NET formation as that we detected both in vitro and in vivo, in association with signs of endothelial damage. We propose SPARC as a new potential marker of MDSC, in both human and mouse, with the additional feature of controlling MDSC suppressive activity while preventing an excessive inflammatory state through the control of NF-kB signaling pathway

Exploring the photothermo-catalytic performance of brookite tio2-ceo2 composites

The thermocatalytic, photocatalytic and photothermo-catalytic oxidation of some volatile organic compounds (VOCs), 2-propanol, ethanol and toluene, was investigated over brookite TiO2-CeO2 composites. The multi-catalytic approach based on the synergistic effect between solar photocatalysis and thermocatalysis led to the considerable decrease in the conversion temperatures of the organic compounds. In particular, in the photothermo-catalytic runs, for the most active samples (TiO2-3 wt% CeO2 and TiO2-5 wt% CeO2). the temperature at which 90% of VOC conversion occurred was about 60◦ C, 40◦ C and 20◦ C lower than in the thermocatalytic tests for 2-propanol, ethanol and toluene, respectively. Furthermore. the addition of cerium oxide to brookite TiO2 favored the total oxidation to CO2 already in the photocatalytic tests at room temperature. The presence of small amounts of cerium oxide allowed to obtain efficient brookite-based composites facilitating the space charge separation and increasing the lifetime of the photogenerated holes and electrons as confirmed by the characterization measurements. The possibility to concurrently utilize the photocatalytic properties of brookite and the redox properties of CeO2, both activated in the photothermal tests, is an attractive approach easily applicable to purify air from VOCs

A solar photothermocatalytic approach for the CO2 conversion: Investigation of different synergisms on CoO-CuO/brookite TiO2-CeO2 catalysts

The photoactive features of the least common polymorph of TiO2, i.e. brookite, were combined with the thermocatalytic redox ones of cerium oxide, focusing on the effects of the addition of small amounts of Co-Cu oxides for the solar CO2 conversion. By considering the characterization data, a surface segregation of the hosted metal oxides on the TiO2-CeO2 composite was evidenced, and their presence increased the amount of oxygen vacancies and improved the charge carriers separation. The bimetallic oxides-based sample was the most performing one in the photocatalytic carbon dioxide reduction at room temperature. The formation of carbon monoxide and methane was 5 and 0.5 μmol g−1h−1, respectively, i.e. about 10 times higher than that found with bare brookite. A further enhancement was obtained with the same CoO-CuO/TiO2-CeO2 catalyst applying the photothermal approach. The CO2-TPD and the FTIR measurements highlighted the high interaction between CO2 and the surface sites

Molecular Structures in T=1 states of 10B

Multi-center (molecular) structures can play an important role in light nuclei. The highly deformed rotational band in 10Be with band head at 6.179 MeV has been observed recently and suggested to have an exotic alpha:2n:alpha configuration. A search for states with alpha:pn:alpha two-center molecular configurations in 10B that are analogous to the states with alpha:2n:alpha structure in 10Be has been performed. The T=1 isobaric analog states in 10B were studied in the excitation energy range of E=8.7-12.1 MeV using the reaction 1H(9Be,alpha)6Li*(T=1, 0+, 3.56 MeV). An R-matrix analysis was used to extract parameters for the states observed in the (p,alpha) excitation function. Five T=1 states in 10B have been identified. The known 2+ and 3- states at 8.9 MeV have been observed and their partial widths have been measured. The spin-parities and partial widths for three higher lying states were determined. Our data support theoretical predictions that the 2+ state at 8.9 MeV (isobaric analog of the 7.54 MeV state in 10Be) is a highly clustered state and can be identified as a member of the alpha:np:alpha rotational band. The next member of this band, the 4+ state, has not been found. A very broad 0+ state at 11 MeV that corresponds to pure alpha+6Li(0+,T=1) configuration is suggested and it might be related to similar structures found in 12C, 18O and 20Ne.Comment: 10 pages, 10 figures, accepted in Physical Review

Shedding Light on the Microbial Community of the Macropod Foregut Using 454-Amplicon Pyrosequencing

Twenty macropods from five locations in Queensland, Australia, grazing on a variety of native pastures were surveyed and the bacterial community of the foregut was examined using 454-amplicon pyrosequencing. Specifically, the V3/V4 region of 16S rRNA gene was examined. A total of 5040 OTUs were identified in the data set (post filtering). Thirty-two OTUs were identified as 'shared' OTUS (i.e. present in all samples) belonging to either Firmicutes or Bacteroidetes (Clostridiales/Bacteroidales). These phyla predominated the general microbial community in all macropods. Genera represented within the shared OTUs included: unclassified Ruminococcaceae, unclassified Lachnospiraceae, unclassified Clostridiales, Peptococcus sp. Coprococcus spp., Streptococcus spp., Blautia sp., Ruminoccocus sp., Eubacterium sp., Dorea sp., Oscillospira sp. and Butyrivibrio sp. The composition of the bacterial community of the foregut samples of each the host species (Macropus rufus, Macropus giganteus and Macropus robustus) was significantly different allowing differentiation between the host species based on alpha and beta diversity measures. Specifically, eleven dominant OTUs that separated the three host species were identified and classified as: unclassified Ruminococcaceae, unclassified Bacteroidales, Prevotella spp. and a Syntrophococcus sucromutans. Putative reductive acetogens and fibrolytic bacteria were also identified in samples. Future work will investigate the presence and role of fibrolytics and acetogens in these ecosystems. Ideally, the isolation and characterization of these organisms will be used for enhanced feed efficiency in cattle, methane mitigation and potentially for other industries such as the biofuel industry

Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study

Background Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. Methods Patients with primary triple negative breast cancer 2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. Results In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2–5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. Conclusions Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial–mesenchymal transition, claims for further investigation. Trial registration EU Clinical Trial Register, EudraCT number 2012-004956-12

Nuclear astrophysics and resonant reactions: Exploring the threshold region with the Trojan Horse Method

Resonant reactions play an important role in astrophysics as they might significantly enhance the cross section with respect to the direct reaction contribution and alter the nucleosynthetic flow. Moreover, resonances bear information about states in the intermediate compound nucleus formed in the reaction. However, nuclear reactions in stars take place at energies well below [Formula: see text] MeV and the Coulomb barrier, exponentially suppressing the cross section, and the electron screening effect, due to the shielding of nuclear charges by atomic electrons, make it very difficult to provide accurate input data for astrophysics. Therefore, indirect methods have been introduced; in particular, we will focus on the Trojan Horse Method. We will briefly discuss the theory behind the method, to make clear its domain of applicability, the advantages and the drawbacks, and two recent cases will be shortly reviewed: the [Formula: see text] reaction, which is an important fluorine destruction channel in the proton-rich outer layers of asymptotic giant branch (AGB) stars, and the [Formula: see text] reactions, which play a critical role in astrophysics to understand stellar burning scenarios in carbon-rich environments

Measurement of the 20 and 90 keV resonances in the 18O(p,α)15{}^{18}{\rm O}(p,\alpha){}^{15}N reaction via THM

The $^{18}{\rm O}(p,\alpha)^{15}{\rm N}$ reaction is of primary importance in several astrophysical scenarios, including fluorine nucleosynthesis inside AGB stars as well as oxygen and nitrogen isotopic ratios in meteorite grains. Thus the indirect measurement of the low energy region of the $^{18}{\rm O}(p,\alpha)^{15}{\rm N}$ reaction has been performed to reduce the nuclear uncertainty on theoretical predictions. In particular the strength of the 20 and 90 keV resonances have been deduced and the change in the reaction rate evaluated.Comment: 4 pages, 4 figures, submitted to PR