Influence of innate immunity on cancer cell stemness

Even if cancer stem cells (CSCs) represent only a small proportion of the tumor mass, they significantly account for tumor maintenance, resistance to therapies, relapse and metastatic spread, due to their increased capacity of self-renewal, multipotency, tumorigenicity and quiescence. Emerging evidence suggests that the immune contexture within the tumor microenvironment (TME) determines both the response to therapy and the clinical outcome. In this context, CSCs acquire immune evasion skills by editing immune cell functions and sculpting the immunosuppressive landscape of TME. Reciprocally, infiltrating immune cells influence CSCs self-renewal, tumorigenicity and metastasis. In this review, we summarize the immunomodulatory properties of CSCs, as well as the impact of innate immune cells on cancer cells stemness in the different phases of cancer immunoediting process and neoplastic progression

Techno-economic assessment of SEWGS technology when applied to integrated steel-plant for CO2 emission mitigation

Mitigation of CO2 emissions in the industrial sector is one of the main climate challenges for the coming decades. This work, carried out within the STEPWISE H2020 project, performs a preliminary techno-economic assessment of the Sorption Enhanced Water Gas Shift (SEWGS) technology when integrated into the iron and steel plant to mitigate CO2 emissions. The SEWGS separates the CO2 from the iron and steel off-gases with residual energy content (i.e. Blast Furnace Gas, Basic Oxygen Furnace Gas and Coke Oven Gas) and the produced H2 is sent to the power generation section to produce the electricity required by the steel plant, while the CO2 is compressed and transported for storage. Detailed mass and energy balances are performed together with a SEWGS cost estimation to assess the energy penalty and additional costs related to CO2 capture. Results demonstrates the potential of SEWGS to capture over 80 % of CO2 in the off-gases, which results in entire plant CO2 emission reduction of 40 % with a Specific Energy Consumptions for CO2 Avoided (SPECCA) around 1.9 MJ/kgCO2. SEWGS outperforms a commercial amine scrubbing technology which has a SPECCA of 2.5 MJ/kgCO2 and only 20 % of CO2 avoided. The cost of CO2 avoided calculated on the basis of a fully integrated steel plant is around 33 €/tCO2 compared to 38 €/tCO2 of the amine technology

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

Assessing the potential of molten carbonate fuel cell-based schemes for carbon capture in natural gas-fired combined cycle power plants

Abstract This work explores two configurations of natural gas-fired combined cycles (NGCC) with molten carbonate fuel cells (MCFC) for CO2 capture. Special attention is devoted to the selection of MCFC operating conditions (trade-off between CO2 capture and voltage losses), heat integration scheme, fuel use and CO2 purification. Two schemes are considered: (i) in the first "integrated" scheme, MCFC modules are installed between the gas turbine and the heat recovery steam generator (HRSG) to maximize the efficiency of the integrated power plant; (ii) in the second "non-integrated" layout, the MCFC is located downstream of the HRSG and a regenerative heat exchanger is designed to preheat cathode reactants up to the MCFC working temperature. This study includes a full techno-economic analysis of the two layouts based on a preliminary sizing of the key-components, and a sensitivity analysis on the CO2 utilization factor. Compared to a benchmark amine scrubbing process, the "integrated" configuration shows considerably better performance (Specific Primary Energy Consumption for CO2 Avoided - SPECCA = 0.31 MJ kgCO2-1; Cost of CO2 avoided - CCA = 50 $tCO2−1), whereas the "non-integrated" solution shows higher energy penalties but similar CO2 avoidance cost (SPECCA = 2.4  MJ  kgCO2−1; CCA = 76$ tCO2−1)

Overexpression of Osmyb4 enhances compatible solute accumulation and increases stress tolerance of arabidopsis thaliana

In this paper, we report the metabolic and molecular changes in response to cold and drought induced in Osmyb4 transgenic Arabidopsis thaliana compared with the wildtype (WT). The rice Osmyb4 gene codes for a transcription factor (Myb4) induced by cold treatment and, in Arabidopsis transgenic plants, improves cold and freezing tolerance [Vannini C, Locatelli F, Bracale M, Magnani E, Marsoni M, Osnato M, Mattana M, Baldoni E, Coraggio I (2004) Plant J 37: 115-127]. Here, we report the ability of Myb4 to induce also drought tolerance in Arabidopsis transgenic plants. By the use of nuclear magnetic resonance (NMR) and enzymatic assays, we showed that several compatible solutes (glucose, fructose, sucrose, proline, glycine betaine and sinapoyl malate) accumulate in higher amount in Osmyb4-overexpressing plants with respect to the WT, both under normal and stress conditions. Considering proline, we also found that in transgenic plants the levels of the mRNAs coding for \u3941- pyrroline-5-carboxylate synthase (EC not assigned) and for \u3941- pyrroline-5-carboxylate dehydrogenase (EC 1.5.1.12) were higher and lower, respectively. The constitutive activation of several stress-inducible pathways and different kinetics in the accumulation of several metabolites, in Myb4 transgenic plants, may represent an advantage to prepare plants to face the stress condition. Moreover, these results taken together suggest that Myb4 integrates the activation of multiple components of stress response

Myeloid-derived suppressor cells: Ductile targets in disease

Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells with major regulatory functions and rise during pathological conditions, including cancer, infections and autoimmune conditions. MDSC expansion is generally linked to inflammatory processes that emerge in response to stable immunological stress, which alter both magnitude and quality of the myelopoietic output. Inability to reinstate physiological myelopoiesis would fall in an "emergency state" that perpetually reprograms myeloid cells toward suppressive functions. While differentiation and reprogramming of myeloid cells toward an immunosuppressive phenotype can be considered the result of a multistep process that originates in the bone marrow and culminates in the tumor microenvironment, the identification of its driving events may offer potential therapeutic approaches in different pathologies. Indeed, whereas expansion of MDSCs, in both murine and human tumor bearers, results in reduced immune surveillance and antitumor cytotoxicity, placing an obstacle to the effectiveness of anticancer therapies, adoptive transfer of MDSCs has shown therapeutic benefits in autoimmune disorders. Here, we describe relevant mechanisms of myeloid cell reprogramming leading to generation of suppressive MDSCs and discuss their therapeutic ductility in disease

Amyotrophic lateral sclerosis incidence following exposure to inorganic selenium in drinking water

Background and aim. Some laboratory and epidemiologic studies have documented an association between high intake of the trace element selenium and risk of amyotrophic lateral sclerosis (ALS), a degenerative disease of the motor neurons. There have been few epidemiologic studies of the association. Methods. From 1986 through 2015, we followed a community cohort in northern Italy that had been inadvertently exposed in the 1974-86 period to drinking water with unusually high levels of selenium, around 8 µg/ml, in its inorganic hexavalent form (selenate). In this cohort, we previously identified a high incidence of ALS during 1986-94. Here we report extended follow-up of this exposed cohort, as well as of an unexposed cohort including over 95,000 municipal residents, for an additional 21 years. We identified incident cases through administrative sources and a specialized registry. Results. During follow-up, 7 and 112 ALS cases were newly diagnosed in the exposed and unexposed cohorts, respectively, yielding incidence rates of 14 and 5 per 100,000 person-years. A Poisson regression analysis adjusting for age, sex, and calendar year produced an overall rate ratio (RR) for ALS of 2.8 (95% confidence interval (CI) 1.3 - 6) in the entire period of follow-up. The association was stronger earlier than later in follow-up (1986-1994 vs. 1994-2015), and among women than men. All exposed cases were of the sporadic, non-familial form for the disease. Conclusion. Overall, results from this ‘natural experiment’ indicate a positive association between chronic exposure to inorganic selenium and ALS incidence, with rates in the exposed cohort declining over time after cessation of exposure. Also taking into account the recognized neurotoxicity of selenium, particularly its selective toxicity on motor neurons observed in animal studies, the present study provides additional support for the hypothesis that selenium in its inorganic form increases ALS risk

MOLECULAR HOMOLOGY AMONG MEMBERS OF THE R-GENE FAMILY IN MAIZE

The R gene family determines the timing, distribution and amount of anthocyanin pigmentation in maize. This family comprises a set of regulatory genes, consisting of a cluster of several elements at the R locus, on chromosome 10, the Lc and Sn gene lying about two units R distal and B on chromosome 2. Each gene determines a tissue-specific pigmentation of different parts of the seed and plant. The proposed duplicated function of R, Sn, Lc and B loci is reflected in cDNA sequence similarity. In this paper an extensive analysis of the predicted proteins of the R, Sn, Lc and B genes together with a search for putative sites of post-translational modification is reported. A comparison with the PROSITE database discloses several N-glycosylation and phosphorylation sites, as well as the basic Helix-Loop-Helix (HLH) domain of transcriptional activators. Sn, Lc, and R-S show a high conservation of these sites, while B is more divergent. Analysis of the 5' leader of mRNA sequences discloses the presence of five ATG triplets with two upstream open reading frames (uORFs) of 38 and 15 amino acids and a loop structure indicating a possible mechanism of control at the translational level. It is conceivable that possible mechanisms acting at the translational and post-translational level could modulate the expression and the activation of these transcription factors. Northern analysis of various tissues of different R alleles highlights a strict correlation between pigment accumulation in different tissues and the expression of the regulatory and structural genes suggesting that the pattern of pigmentation relies on a mechanism of differential expression of the members of the R family. Analysis of the Sn promoter discloses the presence of several sequences resembling binding sites of known transcription factors (as GAGA and GT) that might be responsible for the spatial and light-induced expression of this gene. Two regions include a short sequence homologous to the consensus binding site of the B-HLH domain suggesting a self-regulatory control of the Sn gene