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The work is a case study of a cruise ship supplied by liquefied natural gas (LNG) and equipped with a solid oxide fuel cell (SOFC). It is supposed that a 20 MW SOFC plant is installed on-board to supply hotel loads and assisting three dual-fuel (DF) diesel/LNG generator sets. LNG consumption and emissions are estimated both for the SOFC plant and DF generator sets. It results that the use of LNG-SOFC plant in comparison to DF generator sets allows to limit significantly the SOx, CO, NOx, PM emissions and to reduce the emission of CO2 by about 11%. A prediction of the weight and volume of the SOFC plant is conducted and a preliminary modification of the general arrangement of the cruise ship is suggested, according to the latest international rules. It results that the SOFC plant is heavier and occupies more volume on board than a DF gen-set; nevertheless, these features do not affect the floating and the stability of the cruise ship.

In humans, the family of Bcl-2 associated athanogene (BAG) proteins includes six members characterized by exceptional multifunctionality and engagement in the pathogenesis of various diseases. All of them are capable of interacting with a multitude of often unrelated binding partners. Such binding promiscuity and related functional and pathological multifacetedness cannot be explained or understood within the frames of the classical "one protein-one structure-one function" model, which also fails to explain the presence of multiple isoforms generated for BAG proteins by alternative splicing or alternative translation initiation and their extensive posttranslational modifications. However, all these mysteries can be solved by taking into account the intrinsic disorder phenomenon. In fact, high binding promiscuity and potential to participate in a broad spectrum of interactions with multiple binding partners, as well as a capability to be multifunctional and multipathogenic, are some of the characteristic features of intrinsically disordered proteins and intrinsically disordered protein regions. Such functional proteins or protein regions lacking unique tertiary structures constitute a cornerstone of the protein structure-function continuum concept. The aim of this paper is to provide an overview of the functional roles of human BAG proteins from the perspective of protein intrinsic disorder which will provide a means for understanding their binding promiscuity, multifunctionality, and relation to the pathogenesis of various diseases.

SUMMARYThe early steps of viral infection involve protein complexes and structural lipid rearrangements, which mark the characteristic strategies of each virus in entering permissive host cells. Human IFITM proteins have been described as inhibitors of a broad range of viruses. Despite their homology and functional redundancy, recently it has been surprisingly shown that SARS-CoV-2 is able to specifically hijack the IFITM2 protein. Here has been reported the characterization of a newly generated specific anti-IFITM2 mAb able to impair SARS-CoV-2 Spike protein internalization and, consequently, to reduce the SARS-CoV-2 cytopathic effects and syncytia formation. Importantly, as evidence of the more general involvement of IFITM2 in virus entry, the anti-IFITM2 mAb was able to efficiently reduce HSVs- and RSV-dependent cytopathic effects. Hence, IFITM proteins could be promising targets that can foster the development of biological antiviral molecules, or suggest additional therapeutic strategies for the treatment of viral infections.GRAPHICAL ABSTRACT

BAG3 is highly expressed across cancer types and its intracellular activity is critical for cancer cell survival. However, recent findings suggest that BAG3 can also modulate the tumor microenvironment to promote cancer progression and resistance to therapies, suggesting new ways to target this protein in cancer therapy.

Hypoxia and angiogenesis in solid tumors are often strictly linked to the development of fibrotic tissues, a detrimental event that compromises the antitumor immunity. As a consequence, tumor aggressiveness and poor patient prognosis relate to higher incidence of tissue fibrosis and stromal stiffness. The molecular pathways through which normal fibroblasts are converted in cancer-associated fibroblasts (CAFs) have a central role in the onset of fibrosis in tumor stroma, thus emerging as a strategic target of novel therapeutic approaches for cancer disease. Several studies addressed the role of BAG3 in sustaining growth and survival of cancer cell and also shed light on the different mechanisms in which the intracellular protein is involved. More recently, new pieces of evidence revealed a pivotal role of extracellular BAG3 in pro-tumor cell signaling in the tumor microenvironment, as well as its involvement in the development of fibrosis in tumor tissues. Here we report further data showing the presence of the BAG3 receptor (Interferon-induced transmembrane protein [IFITM]-2) on the plasma membrane of normal dermal fibroblasts and the activity of BAG3 as a factor able to induce the expression of α-smooth muscle actin and the phosphorylation of AKT and focal adhesion kinase, that sustain CAF functions in tumor microenvironment. Furthermore, in agreement with these findings, bag3 gene expression has been analyzed by high throughput RNA sequencing databases from patients-derived xenografts. A strong correlation between bag3 gene expression and patients' survival was found in several types of fibrotic tumors. The results obtained provide encouraging data that identify BAG3 as a promising therapeutic target to counteract fibrosis in tumors.

Pancreatic ductal adenoma carcinoma (PDAC) is considered one of the deadliest solid cancers as it is usually diagnosed in advanced stages and has a poor response to treatment. The enormous effort made in the last 2 decades in the oncology field has not led to significant progress in improving early diagnosis or therapy for PDAC. The stroma of PDAC plays an active role in tumour initiation and progression and includes immune cells and stromal cells. We previously reported that Bcl2-associated athanogene (BAG3) secreted by PDAC cells activates tumour-associated macrophages to promote tumour growth. The disruption of this tumour-stroma axis by the anti-BAG3 H2L4 therapeutic antibody is sufficient to delay tumour growth and limit metastatic spreading in different PDAC preclinical models. In the present study, we examined the role of BAG3 to activate human fibroblasts (HF) in releasing cytokines capable of supporting tumour progression. Treatment of fibroblasts with recombinant BAG3 induced important changes in the organisation of the cytoskeleton of these cells and stimulated the production of interleukin-6, monocyte chemoattractant protein-1/C-C motif chemokine ligand 2, and hepatocyte growth factor. Specifically, we observed that BAG3 triggered a depolymerisation of microtubules at the periphery of the cell while they were conserved in the perinuclear area. Conversely, the vimentin-based intermediate filaments increased and spread to the edges of the cells. Finally, the conditioned medium (CM) collected from BAG3-treated HF promoted the survival, proliferation, and migration of the PDAC cells. Blocking of the PDAC-fibroblast axis by the H2L4 therapeutic anti-BAG3 antibody, resulted in inhibition of cytokine release and, consequently, the inhibition of the migratory phenotype conferred by the CM to PDAC cells.

The BAG3- and SIRPα- mediated pathways trigger distinct cellular targets and signaling mechanisms in pancreatic cancer microenvironment. To explore their functional connection, we investigated the effects of their combined blockade on cancer growth in orthotopic allografts of pancreatic cancer mt4–2D cells in immunocompetent mice. The anti-BAG3 + anti-SIRPα mAbs treatment inhibited (p = 0.007) tumor growth by about the 70%; also the number of metastatic lesions was decreased, mostly by the effect of the anti-BAG3 mAb. Fibrosis and the expression of the CAF activation marker α-SMA were reduced by about the 30% in animals treated with anti-BAG3 mAb compared to untreated animals, and appeared unaffected by treatment with the anti-SIRPα mAb alone; however, the addition of anti-SIRPα to anti-BAG3 mAb in the combined treatment resulted in a > 60% (p p p

BAG3, a member of the BAG family of co-chaperones, is a multidomain protein with a role in several cellular processes, including the control of apoptosis, autophagy and cytoskeletal dynamics. The expression of bag3 is negligible in most cells but can be induced by stress stimuli or malignant transformation. In some tumours, BAG3 has been reported to promote cell survival and resistance to therapy. The expression of BAG3 has been documented in ovarian, endometrial and cervical cancers, and studies have revealed biochemical and functional connections of BAG3 with proteins involved in the survival, invasion and resistance to therapy of these malignancies. BAG3 expression has also been shown to correlate with the grade of dysplasia in squamous intraepithelial lesions of the uterine cervix. Some aspects of BAG3 activity, such as its biochemical and functional interaction with the human papillomavirus proteins, could help in our understanding of the mechanisms of oncogenesis induced by the virus. This review aims to highlight the potential value of BAG3 studies in the field of gynaecological tumours.

Aberrant p53 immunohistochemical expression is used to identify the copy-number-high/TP53-mutant subgroup of endometrial cancer (EC). We aimed to determine the diagnostic accuracy of p53 immunohistochemistry as surrogate for TP53 sequencing through a systematic review and meta-analysis. Electronic databases were searched from their inception to June 2019. All studies assessing p53 expression and TP53 mutations in EC were included. Diagnostic accuracy was assessed based on area under the curve (AUC). Immunohistochemical criteria used to define aberrant p53 expression were “overexpression” and “overexpression or complete absence”. Subgroup analysis was based on the sequencing technique adopted (Polymerase Chain Reaction + sequencing, or next generation sequencing, NGS). Thirteen observational studies with 727 endometrial cancers were included. Both “overexpression” and “overexpression or complete absence” showed high diagnostic accuracy (AUC = 0.9088 and 0.9030, respectively). The subgroup with “overexpression” and NGS showed the best results, with very high diagnostic accuracy (AUC = 0.9927). In conclusion, immunohistochemistry for p53 is a highly accurate surrogate of TP53 sequencing. Overexpression of p53 in ≥70−80% showed the best accuracy in predicting TP53 mutations. Further studies in this field should adopt optimized immunohistochemical procedures and take into account less common p53 patterns (e.g. cytoplasmic expression).

The paper aims to make the state of the art on the applications of Fuel Cells (FCs) in maritime applications. It synthetically describes the Solid Oxide Fuel Cells and Molten Carbonate Fuel Cells technologies highlighting critical issues and advantages dealing with the maritime sectors. Several projects have been described in literature, the main focus are the assessments of potential for FC use, rules development, feasibility studies and concept design for testing FCs in various vessels. Low temperature FCs, in particular PEMFC fuelled by H2, are suitable for small and medium applications, high temperature FCs (HTFCs) for larger ones. The main conclusions are that no fundamental obstacles for the integration of FC-systems into commercial ships exist as well as no fundamental obstacles with respect to safety.

BAG3 is a multifunctional protein that can bind to heat shock proteins (Hsp) 70 through its BAG domain and to other partners through its WW domain, proline-rich (PXXP) repeat and IPV (Ile-Pro-Val) motifs. Its intracellular expression can be induced by stressful stimuli, while is constitutive in skeletal muscle, cardiac myocytes and several tumour types. BAG3 can modulate the levels, localisation or activity of its partner proteins, thereby regulating major cell pathways and functions, including apoptosis, autophagy, mechanotransduction, cytoskeleton organisation, motility. A secreted form of BAG3 has been identified in studies on pancreatic ductal adenocarcinoma (PDAC). Secreted BAG3 can bind to a specific receptor, IFITM2, expressed on macrophages, and induce the release of factors that sustain tumour growth and the metastatic process. BAG3 neutralisation therefore appears to constitute a novel potential strategy in the therapy of PDAC and, possibly, other tumours.

Gut microbiota, a group of 1014 bacteria, eukaryotes and virus living in gastrointestinal tract, is crucial for many physiological processes in particular plays an important role in inflammatory and immune reactions. Several internal and external factors can influence this population, and shifts in their composition, have been demonstrated to contribute and affect different diseases. During dysbiosis several bacteria related to inflammation, one of the most necessary factors in carcinogenesis; it has been shown that some bacterial strains through deregulation of different signals/pathways may affect tumor development through the production of many factors. Gut microbiota might be considered as a holistic hub point for cancer development: direct and indirect involvements have been studying in several neoplasms such as colon rectal cancer, hepatocellular carcinoma and breast cancer. This review discuss over the evidence of crosstalk between gut microbiota and cancer, its ability to modulate chemotherapy, radiotherapy and immunotherapy, and the possibility that the intestinal microbial is a new target for therapeutic approaches to improve the prognosis and quality of life of cancer patients.

The biohydrogen production by dark fermentation (DF) of Arundo donax enzymatic hydrolysate, obtained from untreated (ADH) and steam-exploded (ADHexp) biomass, was investigated. A glucose synthetic medium (SM) was also studied for comparison. The main novelty of the manuscript is the use of a new methodology for the selection of H2 producing bacteria at detriment of the methanogenic ones that does not require harsh physico-chemical treatments of the source anaerobic consortium. DF tests were carried out under mesophilic conditions (38 °C) in batch reactors. A mixed culture from an anaerobic digestion plant was used as inoculum for all substrates. The inoculum was pre-cultured in nutrient medium and the progressive adaptation of bacterial consortium to hydrogen production was followed in three sequenced batch tests. In all tests H2 production is maximal in the first 24 h (in parallel to microbial growth). Cumulative H2 volumes approximately double with the progressive adaptation of the microbial consortium. H2 yields obtained after the third batch set on SM, ADH, and ADHexp were 2.00, 3.06, 2.59 ( mol H 2 / mol glucose ) respectively. H2 yields obtained were comparable or higher than literature data confirming the effectiveness of the experimental procedure employed in selecting H2 producers.

BAG3 is a member of human BAG (Bcl-2-associated athanogene) proteins and plays a role in apoptosis, cell adhesion, cytoskeleton remodeling, and autophagy. The aim of this study was to evaluate BAG3 levels in healthy subjects, hypertensive patients, and hypertensive diabetic patients. We enrolled 209 Caucasian adults, of both sex, 18-75 years of age, 77 were healthy controls, 62 were affected by hypertension, and 70 were affected by hypertension and type 2 diabetes. All patients underwent an assessment that included medical history, physical examination, vital signs, a 12-lead electrocardiogram, measurements of systolic (SBP), and diastolic blood pressure (DBP), heart rate (HR), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c ), triglycerides (TG), transaminases, high sensitivity C-reactive protein (Hs-CRP), and BAG3. We observed higher blood pressure values in hypertensive, and hypertensive diabetic patients compared to controls. As expected, FPG and HbA1c were higher in diabetic hypertensive patients, compared to the other two groups. No Tg levels differences were recorded among the three groups. Hs-CRP was higher in diabetic hypertensive patients compared to healthy subjects. Finally, BAG3 levels were higher in hypertensives, and hypertensive diabetic patients compared to controls. We observed higher levels of BAG3 in hypertensive patients compared to healthy controls, and even higher levels in hypertensive diabetic patients compared to healthy subjects. This paper could be the first of a long way to identify potential involvement of deregulated BAG3 levels in cardiometabolic diseases.

// Luana Guerriero 1 , Giuseppe Palmieri 2 , Margot De Marco 1 , Antonio Cossu 3 , Paolo Remondelli 4 , Mario Capunzo 4 , Maria Caterina Turco 1, 4 and Alessandra Rosati 1, 4 1 BIOUNIVERSA s.r.l., 84084 Baronissi, Italy 2 Unit of Cancer Genetics, Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), 07100 Sassari, Italy 3 Unit of Pathology, Azienda Ospedaliero Universitaria (AOU), University di Sassari, 07100 Sassari, Italy 4 Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana” University of Salerno, 84084 Baronissi, Italy Correspondence to: Alessandra Rosati, email: arosati@unisa.it Keywords: BAG3, melanoma, BRAF, vemurafenib, resistance Received: January 20, 2017 Accepted: June 13, 2017 Published: June 30, 2017 ABSTRACT BAG3 protein, a member of BAG family of co-chaperones, has a pro-survival role in several tumour types. BAG3 anti-apoptotic properties rely on its characteristic to bind several intracellular partners, thereby modulating crucial events such as apoptosis, differentiation, cell motility, and autophagy. In human melanomas, BAG3 positivity is correlated with the aggressiveness of the tumour cells and can sustain IKK-γ levels, allowing a sustained activation of NF-κB. Furthermore, BAG3 is able to modulate BRAFV600E levels and activity in thyroid carcinomas. BRAFV600E is the most frequent mutation detected in malignant melanomas and is targeted by Vemurafenib, a specific inhibitor found to be effective in the treatment of advanced melanoma. However, patients with BRAF-mutated melanoma may result insensitive ab initio or, mostly, develop acquired resistance to the treatment with this molecule. Here we show that BAG3 down-modulation interferes with BRAF levels in melanoma cells and sensitizes them to Vemurafenib treatment. Furthermore, the down-modulation of BAG3 protein in an in vitro model of acquired resistance to Vemurafenib can induce sensitization to the BRAFV600E specific inhibition by interfering with BRAF pathway through reduction of ERK phosphorylation, but also on parallel survival pathways. Future studies on BAG3 molecular interactions with key proteins responsible of acquired BRAF inhibitor resistance may represent a promising field for novel multi-drugs treatment design.

BAG3 protein has emerged as a key regulator of important cellular processes and its expression is increased in some tumor types; however, despite its potential value for future chemotherapeutics, no selective BAG3 modulators have been yet reported. Here we report the 2,4-thiazolidinedione derivative 28 as the first BAG3 protein modulator.

Chaperone-assisted selective autophagy (CASA) is a newly-described selective tension-induced macroautophagy pathway mediated by Bag3 that is believed to be essential for mechanotransduction in skeletal muscle and to be an important regulator of the immune system. We investigated CASA machinery both in healthy and in fifteen papillomavirus-associated neoplastic bovine urothelium. The components of CASA complex, that comprises the molecular chaperones HspA8/Hsc70 and Hsp8B/Hsp22 and the cochaperones Bag3 and STUB1/CHIP, were studied by molecular, microscopic and submicroscopic investigations. CASA complex was found to be constitutively expressed in healthy bovine urothelium; its expression increased in urothelial cancers of cattle, namely thirteen papillary carcinomas and two papillary urothelial neoplasm of low malignant potential (PUNLMPs). We suggest that basal levels of CASA are important in the healthy urothelium which interfaces with the community of urinary microbiota thus representing an important epithelial cell-autonomous mechanism of antibacterial defense. Co-immunoprecipitation studies using an antibody against bovine papillomavirus E5 protein revealed that the oncoprotein co-localized with CASA complex in urothelial cancer cells. This suggests that infection by BPV E5 could influence cell behaviour by interfering with basal autophagy processes although this study did not conclusively show that this interaction increased the expression of CASA proteins. In neoplastic urothelium, CASA could be involved in regulating fundamental cellular processes such adhesion, migration, and proliferation and so might influence the biological behaviour of urothelial tumors in cattle.

A 13X zeolite modified with Cu ions (13X Ex-Cu) by means of an innovative technique was employed as adsorbent for H2S removal from biogas, to obtain a desulfurized fuel suitable for molten carbonate fuel cell systems. Sorbent performance was characterized over a wide range of operating conditions typical of biogas mixtures (high H2S content - 200 and 1000 ppmv; CH4 (60%)/CO2 (40%) matrices) and compared to several conventional sorbents. A sensitivity performance analysis was conducted, varying parameters as space velocity, reactor temperature, gas matrix composition and particles size, finalized to identify the optimal conditions for the studied application. 13X Ex-Cu zeolite showed high potentiality for H2S uptake, specifically lowering space velocity, increasing reactor temperature and in presence of high methane concentration in the gas mixture, with adsorption capacity of 40 mg/g under specific and optimized conditions. By means of B.E.T. and XRD analyses, it was demonstrated that the obtained enhanced performance is due to the presence of a large amount of Cu2+ ions, guaranteed by the innovative synthesis procedure, able to realize an efficient physical-chemical adsorption mechanism.

In a recent article, Cho and colleagues highlight the connection between cancer-associated fibroblasts (CAF) and tumor-associated macrophages (TAM) in tumor progression. They show that cancer cell–activated CAFs induced monocyte differentiation into M2-like TAMs via IL6 and GM-CSF release, and

// Francesca Galdiero 1 , Anna Maria Bello 1 , Anna Spina 1 , Anna Capiluongo 1 , Sophie Liuu 2 , Margot De Marco 3 , Alessandra Rosati 3, 4 , Mario Capunzo 4 , Maria Napolitano 1 , Emilia Vuttariello 1 , Mario Monaco 1 , Daniela Califano 1 , Maria Caterina Turco 3, 4, 5 , Gennaro Chiappetta 1 , Joelle Vinh 2 and Giovanni Chiappetta 2 1 Functional Genomic Unit, Istituto Nazionale Tumori–IRCCS–Fondazione G.Pascale, Napoli, Italia 2 ESPCI ParisTech, Spectrometrie de Masse Biologique et Proteomique (SMBP), USR3149 CNRS, Paris, France 3 Biouniversa s.r.l., University of Salerno, Fisciano, Italy 4 Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi (SA), Italy 5 "SS. Giovanni di Dio e Ruggi d'Aragona-Schola Medica Salernitana", University of Salerno Hospital, Salerno, Italy Correspondence to: Gennaro Chiappetta, email: g.chiappetta@istitutotumori.na.it Keywords: BAG3; anaplastic thyroid cancer; SILAC; CAV1; SERPINB2 Received: May 18, 2017 Accepted: October 30, 2017 Published: January 03, 2018 ABSTRACT BAG3 protein is an apoptosis inhibitor and is highly expressed in Anaplastic Thyroid Cancer. We investigated the entire set of proteins modulated by BAG3 silencing in the human anaplastic thyroid 8505C cancer cells by using the Stable-Isotope Labeling by Amino acids in Cell culture strategy combined with mass spectrometry analysis. By this approach we identified 37 up-regulated and 54 down-regulated proteins in BAG3-silenced cells. Many of these proteins are reportedly involved in tumor progression, invasiveness and resistance to therapies. We focused our attention on an oncogenic protein, CAV1, and a tumor suppressor protein, SERPINB2, that had not previously been reported to be modulated by BAG3. Their expression levels in BAG3-silenced cells were confirmed by qRT-PCR and western blot analyses, disclosing two novel targets of BAG3 pro-tumor activity. We also examined the dataset of proteins obtained by the quantitative proteomics analysis using two tools, Downstream Effect Analysis and Upstream Regulator Analysis of the Ingenuity Pathways Analysis software. Our analyses confirm the association of the proteome profile observed in BAG3-silenced cells with an increase in cell survival and a decrease in cell proliferation and invasion, and highlight the possible involvement of four tumor suppressor miRNAs and TP53/63 proteins in BAG3 activity.

Vanadium compounds can exert anticancer effects, partly due to inhibition of tyrosine phosphatases. Here, we report the effect of N,N'-ethylenebis (pyridoxylideneiminato) vanadium (IV) complex (Pyr2 enV(IV)), that induced 93% and 57% of cell mortality in A375 (human melanoma) and A549 (human lung carcinoma) cells, respectively; the mortality was

In this chapter the effects of siloxanes on high-temperature fuel cells have been treated. Siloxanes represent the second largest family of contaminants present in biogas. They derive from a variety of cosmetics, pharmaceuticals, and antifoam products largely and are found mainly in biogas obtained from landfills and wastewater plants. The chemical properties of siloxanes and their concentration in biogas according to site and season variability (typically in the range 2–80 mg/Nm3) have been reported. Most abundant siloxane compounds present in biogas are hexamethyldisiloxane (L2), hexamethylcyclotrisiloxane (D3), octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5). Siloxane impurities can reach downstreams and cause degradation of cell performances due to silica deposition. The mechanisms of silica formation and its interaction with electrodes are illustrated. Among the different techniques for siloxane removal the adsorption is the most practical one today. The commonly used solids, active carbon silica gel, and zeolites are described with several examples giving information on adsorption capacity and breakthrough behavior.

This chapter reviews the biogas production by anaerobic digestion (AD) and thermal gasification (TG) processes. The different steps of the AD and the characteristics of the biogas obtained from kinds of biomass carefully have been described. Some attention is devoted to the study of the conditions and techniques proposed in literature to improve the biogas production from organic waste, also analyzing the treatments of the biomass, such as ultrasound, heating, microwave, and chemicals. The co-digestion technique and the design and operating conditions of digesters have been also taken into account. The TG has been treated describing the whole process and the influence of the operating variables, such as temperature and pressure and gasifying agents. Some examples of the type gasifiers are also given.

This chapter gives a state-of-art of the commercialization process of fuel cells. Fuel cell technology is well established in niche market (military, aerospace) since the second half of nineteenth century, while the commercialization in a larger market is going slowly. Fuel cell systems have been under development for several decades and their applicability has been demonstrated worldwide both in small and in large scale. Nevertheless, successful commercialisation of this technology requires to overcome some barriers. This chapter reviews the main challenges related to the diffusion of fuel cells: low costs, quality and acceptance by end-users. Costs are related to the hydrogen production and manufacturing and depend also by Government’s supports. Technical issues are mainly linked to the robustness, reliability and durability of a fuel cell especially compared to internal combustion or turbine engines. Fortunately, the public acceptance of fuel cell could be easier considering that it is an environment-friendly technological alternative.

This chapter deals with the effect of sulfur compounds on the performances of molten carbonate fuel cells (MCFC). The chapter comprises a brief description of the main components of MCFCs, electrodes and electrolyte. The effects of sulfur compounds on porous nickel-based anode and porous nickel oxide-based cathode are described taking into account also the mechanisms of the interaction electrodes/sulfur compounds, in particular H2S. The interaction of H2S with carbonates of the electrolyte leading to a reduction of active charge carriers has been discussed considering the mechanisms of deactivation.

This chapter synthetically describes the cell technology. The history of fuel cell technology development is briefly described and a comparison between fuel cells and other devices, such as batteries and heat engines, is provided. The advantages of fuel cell technology are discussed taking into account the sectors of application. This chapter also reports the fundamental principles with particular attention to high-temperature fuel cells (MCFC and SOFC) that are emerging in the field of stationary power production as a true alternative to combustion heat engines. The components (electrodes and electrolyte) and most common materials used for MCFC and SOFC are described.

BAG3 is a co-chaperone of the heat shock protein (Hsp) 70, is expressed in many cell types upon cell stress, however, its expression is constitutive in many tumours. We and others have previously shown that in neoplastic cells BAG3 exerts an anti- apoptotic function thus favoring tumour progression. As a consequence we have proposed BAG3 as a target of antineoplastic therapies. Here we identify a novel role for BAG3 in regulation of neo-angiogenesis and show that its downregulation results in reduced angiogenesis therefore expanding the role of BAG3 as a therapeutical target. In brief we show that BAG3 is expressed in endothelial cells and is essential for the interaction between ERK and its phosphatase DUSP6, as a consequence its removal results in reduced binding of DUSP6 to ERK and sustained ERK phosphorylation that in turn determines increased levels of p21 and p15 and cell-cycle arrest in the G1 phase.

Anaplastic thyroid tumors (ATC) express high levels of BAG3, a member of the BAG family of cochaperone proteins that is involved in regulating cell apoptosis through multiple mechanisms.The objective of the study was the investigation of the influence of B-cell lymphoma-2-associated athanogene 3 (BAG3) on ATC growth.We investigated the effects of BAG3 down-modulation, obtained by using a specific small interfering RNA, on in vitro and in vivo growth of the human ATC cell line 8505C. Because BRAF protein plays an important role in ATC cell growth, we analyzed the effects of BAG3 down-modulation on BRAF protein levels. Furthermore, by using a proteasome inhibitor, we verified whether BAG3-mediated regulation of BRAF levels involved a proteasome-dependent mechanism.BAG3 down-modulation significantly inhibits ATC growth in vitro and in vivo. BAG3 coimmunoprecipitates with BRAF protein, and its down-modulation results in a significant reduction of BRAF protein levels, which can be reverted by incubation with the proteasome inhibitor MG132.BAG3 protein sustains ATC growth in vitro and in vivo. The underlying molecular mechanism appears to rely on BAG3 binding to BRAF, thus protecting it from proteasome-dependent degradation. These results are in line with the reported ability of BAG3 to interfere with the proteasomal delivery of a number of other client proteins.

VEGF receptors have been the target of intense research aimed to develop molecules able to inhibit or stimulate angiogenesis. Based on the x-ray structure of the complex placental growth factor-VEGF receptor 1D2, we designed a VEGF receptor-binding peptide reproducing the placental growth factor β-hairpin region Gln87–Val100 that is involved in receptor recognition. A conformational analysis showed that the designed peptide adopts the expected fold in pure water. Moreover, a combination of NMR interaction analysis and cell binding studies were used to demonstrate that the peptide targets VEGF receptors. The VEGF receptor 1D2-interacting residues were characterized at the molecular level, and they correspond to the residues recognizing the placental growth factor sequence Gln87–Val100. Finally, the peptide biological activity was characterized in vitro and in vivo, and it showed a VEGF-like behavior. Indeed, the peptide activated VEGF-dependent intracellular pathways, induced endothelial cell proliferation and rescue from apoptosis, and promoted angiogenesis in vivo. This compound is one of the few peptides known with proangiogenic activity, which makes it a candidate for the development of a novel peptide-based drug for medical applications in therapeutic angiogenesis.

Cu/ZrO 2 catalysts prepared by the sol–gel method were characterized by XRD, N 2 adsorption, DTA/TG, TPR and N 2 O dispersion measurements and tested as catalysts for the oxidative steam reforming of methanol (OSRM). Two synthesis procedures, based on the Cu precursors Cu(CH 3 COO) 2 ·H 2 O ( A -ZrCu samples) and Cu(NO 3 ) 2 ·2.5H 2 O ( N -ZrCu samples) respectively, were compared to investigate the consequence of synthesis parameters on the physical and chemical properties of the prepared materials. The adopted procedures resulted in remarkable differences in thermal behaviour: the crystallization of tetragonal ZrO 2 was shifted to higher temperature in N -ZrCu samples in comparison with pure ZrO 2 , while this effect was not observed in A -ZrCu. XRD data indicated that Cu 2+ ions were incorporated into the ZrO 2 lattice in N -ZrCu samples. Though both synthesis lead to very high surface areas, the textural properties of the reduced samples suggested the existence of different interactions between Cu ions and the ZrO 2 matrix in A -ZrCu and in N -ZrCu. The Cu/ZrO 2 systems showed noticeable catalytic activity for the oxidative steam reforming of methanol, even without the pre-reduction treatment, but the catalytic response is drastically affected by the preparation procedure and the pre-treatments. N -ZrCu samples gave higher methanol conversion and yield to H 2 . Moreover, the distribution of secondary products was completely different: N -ZrCu produced a lot of CO, while A -ZrCu gave large amounts of CH 2 O and (CH 3 ) 2 O.

Despite the progressive increase of early diagnosis, a subset of prostate cancers show a metastasizing and lethal course, not always predictable upon the traditional prognostic parameters. The object of this study was to investigate the role of the survival co-chaperone protein BAG3 as a new prognostic marker for prostate cancer. BAG3 was detected by immunohistochemistry in 55 specimens of surgically removed prostate carcinomas and in 15 surgical specimens of non-neoplastic prostate tissues. Results were compared with clinic-pathological data and outcome of patients and statistically evaluated. BAG3 resulted expressed in all the cases: Non-neoplastic prostate tissue showed a cytoplasmatic staining with apical reinforcement, a finding which appears consistent with the reported connection of the protein with the membrane focal cell-adhesion complexes. In prostate carcinomas, BAG3 showed a progressive decrease of the expression level from well- to low-differentiated carcinoma, coupled with the loss of polarisation of the signal in metastasizing cases. These results indicate that BAG3 intra-cytoplasmic delocalisation is a specific feature of cancer versus non-neoplastic prostate and a candidate new marker for prediction of prostate cancer invasiveness and behaviour.

BAG3, a member of the BAG family of heat shock protein (HSP) 70 cochaperones, is expressed in response to stressful stimuli in a number of normal cell types and constitutively in a variety of tumors, including pancreas carcinomas, lymphocytic and myeloblastic leukemias, and thyroid carcinomas. Down-regulation of BAG3 results in cell death, but the underlying molecular mechanisms are still elusive. Here, we investigated the molecular mechanism of BAG3-dependent survival in human osteosarcoma (SAOS-2) and melanoma (M14) cells. We show thatbag3overexpression in tumors promotes survival through the NF-κB pathway. Indeed, we demonstrate that BAG3 alters the interaction between HSP70 and IKKγ, increasing availability of IKKγ and protecting it from proteasome-dependent degradation; this, in turn, results in increased NF-κB activity and survival. These results identifybag3as a potential target for anticancer therapies in those tumors in which this gene is constitutively expressed. As a proof of principle, we show that treatment of a mouse xenograft tumor model withbag3siRNA-adenovirus that down-regulatesbag3results in reduced tumor growth and increased animal survival.

The immune system is a complex defense mechanism, able to protect the body against pathogens. It consists of a network of cells, tissues, and organs that work together to protect the body. Leukocytes are key operatives of the immune system. Cells destined to become immune cells, like all blood cells, arise in your bodys bone marrow from stem cells (HSC). A large body of evidence show the transcription factors play critical roles in the homeostasis of T cells, B cells, neutrophils and other non-lymphoid leneages. This review discusses the role of the Smek (Suppressor of mek null) gene, that acts in the stress response pathway of animals by binding to and enhancing the transcription of FoxO transcription factors. Furthermore, the review deals with tachykinins, involved in neurotransmission and immune/hematopoietic modulation. Both molecules, objects of recent patents, may have real therapeutic potential.

Cobalt–silicon mixed oxide materials (Co/Si=0.111, 0.250 and 0.428) were synthesised starting from Co(NO3)2·6H2O and Si(OC2H5)4 using a modified sol–gel method. Structural, textural and surface chemical properties were investigated by thermogravimetric/differential thermal analyses (TG/DTA), XRD, UV–vis, FT-IR spectroscopy and N2 adsorption at −196 °C. The nature of cobalt species and their interactions with the siloxane matrix were strongly depending on both the cobalt loading and the heat treatment. All dried gels were amorphous and contained Co2+ ions forming both tetrahedral and octahedral complexes with the siloxane matrix. After treatment at 400 °C, the sample with lowest Co content appeared amorphous and contained only Co2+ tetrahedral complexes, while at higher cobalt loading Co3O4 was present as the only crystalline phase, besides Co2+ ions strongly interacting with siloxane matrix. At 850 °C, in all samples crystalline Co2SiO4 was formed and was the only crystallising phase for the nanocomposite with the lowest cobalt content. All materials retained high surface areas also after treatments at 600 °C and exhibited surface Lewis acidity, due to cationic sites. The presence of cobalt affected the textural properties of the siloxane matrix decreasing microporosity and increasing mesoporosity.

Heat-shock proteins (HSP) 90 exert a relevant role in the survival and response to therapy of many neoplastic cell types. Here, we show that the promoter of hsp90α gene, that encodes the inducible form of HSP90, is regulated by nuclear factor-κB (NF-κB) activity. Indeed, we found that NF-κB factors bound to one of the two putative consensus sequences present in the hsp90α-flanking region; mutation of such motif hampered the phorbol-myristate-13-acetate-stimulated expression of a luciferase reporter gene under the control of the hsp90α promoter. Furthermore, the downmodulation of NF-κB (p65) levels by a specific small interfering (si) RNA resulted in reducing the levels of endogenous HSP90α protein. These findings disclose a previously unrecognized mechanism that contributes to connect NF-κB factors and HSPs in cell defence machinery.

The incidence and death rate of pancreatic ductal adenocarcinoma (PDAC) have increased in recent years, therefore the identification of novel targets for treatment is extremely important. Interactions between cancer and stromal cells are critically involved in tumour formation and development of metastasis. Here we report that PDAC cells secrete BAG3, which binds and activates macrophages, inducing their activation and the secretion of PDAC supporting factors. We also identify IFITM-2 as a BAG3 receptor and show that it signals through PI3K and the p38 MAPK pathways. Finally, we show that the use of an anti-BAG3 antibody results in reduced tumour growth and prevents metastasis formation in three different mouse models. In conclusion, we identify a paracrine loop involved in PDAC growth and metastatic spreading, and show that an anti-BAG3 antibody has therapeutic potential.

Molecular mechanisms protecting cardiomyocytes from stress-induced death, including tension stress, are essential for cardiac physiology and defects in these protective mechanisms can result in pathological alterations. Bcl2-associated athanogene 3 (BAG3) is expressed in cardiomyocytes and is a component of the chaperone-assisted autophagy pathway, essential for homeostasis of mechanically altered cells. BAG3 ablation in mice results in a lethal cardiomyopathy soon after birth and mutations of this gene have been associated with different cardiomyopathies including stress-induced Takotsubo cardiomyopathy (TTC). The pathogenic mechanism leading to TTC has not been defined, but it has been suggested that the heart can be damaged by excessive epinephrine (epi) spillover in the absence of a protective mechanism. The aim of this study was to provide more evidence for a role of BAG3 in the pathogenesis of TTC. Therefore, we sequenced BAG3 gene in 70 TTC patients and in 81 healthy donors with the absence of evaluable cardiovascular disease. Mutations and polymorphisms detected in the BAG3 gene included a frequent nucleotide change g2252c in the BAG3 3′-untranslated region (3′-UTR) of Takotsubo patients (P

Objective To determine whether prolongation of the inflammatory reaction in patients with Behcet's disease (BD) is related to apoptosis resistance and is associated with the up-regulation of antiapoptotic factors. Methods The percentage of cell death was evaluated by flow cytometry in peripheral blood mononuclear cells from 35 patients with BD and 30 healthy volunteers. The expression levels of antiapoptotic factors and NF-κB regulatory proteins were measured using Western blotting and immunohistochemical analyses. To down-regulate NF-κB nuclear translocation, BD T lymphocytes were exposed in vitro to thalidomide and subjected to transfection with NF-κB small interfering RNA. Results Although CD95 is highly expressed in BD T cells, the absence of sensitivity to CD95-induced apoptosis observed may be attributable to the inhibitory action of antiapoptotic genes. Immunoblot analysis for major antiapoptotic proteins showed considerable up-regulation of the short form of cellular FLIP (cFLIP) and Bcl-xL in BD activated T cells, while levels of Bcl-2, caspase 3, and caspase 8 in activated T cells from patients with BD were comparable with those in activated T cells from normal donors. Moreover, expression of IKK and IκB was up-regulated, whereas NF-κB translocated to the nucleus in BD T cells, suggesting that NF-κB activation may modulate the expression of antiapoptotic genes. Interestingly, thalidomide and NF-κB small interfering RNA down-regulated cFLIP and Bcl-xL expression levels and sensitized BD activated T cells to CD95-induced apoptosis. Conclusion Taken together, these results indicate that NF-κB contributes to the regulation of the apoptosis-related factors and death receptors leading to apoptosis resistance in BD T cell subsets. Our results suggest that NF-κB plays a crucial role in the pathogenesis of BD, and that its pharmacologic control could represent a key strategy in modulating specific immune-mediated disease.