Association of cytogenetic abnormalities in a neuroblastoma and fragile sites expression.

A 15 month old boy with a stage IV right suprarenal gland neuroblastoma showed a number of raised biochemical parameters, whilst catecholamines and skeletal survey were normal. Treatment with peptichemio failed to give a clinical response. Histological evidence of neuroblastoma infiltration in the bone marrow aspirate was absent. Immunofluorescence on sedimented cells was negative using antibody UJ223.8, PI153/3 and H11; only UJ308 and to a lesser extent UJ13A gave positive results. After 21 days, however, the same cells in culture showed highly differentiated dendritic processes. Thirty-seven percent metaphases from bone marrow aspirate showed the following karyotype 45XY, del (1) (p32), and two markers. Mar1 = der (2) t (2; 2) (2qter----2q14::2p24----2qter). Mar2 = der (15) t (15; 2) (15qter----15p11::2p11----2pter). Treatment with methotrexate reduced the aberrant mitoses rate to 2%. N-myc in situ hybridisation showed significant signal on both markers confirming the cytogenetic interpretation. Peripheral blood lymphocytes at 72 h showed a higher level of breaks per cell than control. After treatment with aphidicolin (APC) or methotrexate (MTX) for the last 24 h, to induce fragile sites, the incidence of breaks per cells was increased. Moreover 11.4% of APC-induced breaks were in 1p31-32 (mean of normal controls = 2.3%). The mother presented an increased sensitivity to the inducibility of fragile sites, while the father's lymphocytes showed values within the control range. The genetic changes produced by the abnormalities on chromosomes 1 and 2 might be related to tumour progression. Furthermore this is the first description of correlation between a high frequency of fragile site 1p31-32 induced by APC in the patient's lymphocytes and deletion of 1p32 in tumour cells. The interpretation of these findings and of other similar correlations needs further study

Overview and Status of Thermophotovoltaic Systems

Abstract In the last decade thermophotovoltaic (TPV) generator has gained an increasing attention as cogeneration system for the distributed generation sector. Nevertheless, these systems are not fully developed and studied: several aspects need to be further investigated and completely understood. The aim of this study is to give a complete overview and the status of the art of thermophotovoltaic generation considering both the research developments and the experiences field. More in details, in this study, the characteristics of a TPV generator are analyzed with a particular attention to the physical relationships which govern the behavior of its main components. Moreover, the current technologies regarding the combustor, the emitter, the optical filter and the photovoltaic cells are investigated by taking into account both the role of each component and also their integration in the whole system. Finally, a critical review of the realized prototypes is presented and discussed

Optimum sizing of cogeneration plants by means of a genetic algorithm optimization: A case study

In the context of increasing energy consumption, multi-generation systems such as combined heat and power generation (CHP) are attractive to meet the increasingly stringent requirements regarding energy saving in buildings. Hospitals are great consumers of energy, both electrical and thermal: the use of heating and cooling equipment for maintaining satisfactory comfort and indoor air quality for the patients as well as the adoption of several electrical health equipment result in the highest energy consumption per unit floor area of the entire building sector. In the present study, co/tri-generation systems\u2019 optimal set-up, size and operation are investigated for small/medium size hospital facilities. More specifically, after the presentation of the energy consumption profiles for a medium size hospital with 600 beds, set as reference case for this study, a parametric analysis has been carried out varying the peak loads of the user. For each of the proposed scenarios, the optimal plant configuration (sizing of all the energy production systems) has been outlined by means of a numerical code (Trigen 3.0) in-house developed. Afterwards, in order to optimize the load distribution in a smart grid characterized by electrical, thermal, cooling and fuel energy fluxes, an ulterior numerical investigation has been performed. The software, named EGO (Energy Grids Optimizer) consists of a genetic algorithm procedure: it defines the optimal load distribution of a number of energy systems operating into a smart grid based on the minimization of an objective function which expresses the total cost of energy production. Finally, an economic analysis has been carried out in order to evaluate the profitability of the proposed CHP-heat pump scenario

Polyamine oxidase is involved in spermidine reduction of transglutaminase type 2-catalyzed βh-crystallins polymerization in calcium-induced experimental cataract

In an in vitro Ca2+-induced cataract model, the progression of opacification is paralleled by a rapid decrease of the endogenous levels of spermidine (SPD) and an increase of transglutaminase type 2 (TG2, EC 2.3.2.13)-catalyzed lens crystallins cross-linking by protein-boundN(1)-N-8-bis(gamma-glutamyl) SPD. This pattern was reversed adding exogenous SPD to the incubation resulting in a delayed loss of transparency of the rabbit lens. The present report shows evidence on the main incorporation of SPD by the catalytic activity of TG2, toward beta H-crystallins and in particular to the beta B2- and mostly in beta B3-crystallins. The increase of endogenous SPD in the cultured rabbit lens showed the activation of a flavin adenine dinucleotide (FAD)-dependent polyamine oxidases (PAO EC 1.5.3.11). As it is known that FAD-PAO degrades theN(8)-terminal reactive portion ofN(1)-mono(gamma-glutamyl) SPD, the protein-boundN(8)-mono(gamma-glutamyl) SPD was found the mainly available derivative for the potential formation of beta B3-crystallins cross-links by protein-boundN(1)-N-8-bis(gamma-glutamyl)SPD. In conclusion, FAD-PAO degradation of theN(8)-terminal reactive residue of the crystallins boundN(1)-mono(gamma-glutamyl)SPD together with the increased concentration of exogenous SPD, leading to saturation of glutamine residues on the substrate proteins, drastically reducesN(1)-N-8-bis(gamma-glutamyl)SPD crosslinks formation, preventing crystallins polymerization and avoiding rabbit lens opacification. The ability of SPD and MDL 72527 to modulate the activities of TG2 and FAD-PAO involved in the mechanism of lens opacification suggests a potential strategy for the prevention of senile cataract

New immunological potential markers for triple negative breast cancer: IL18R1, CD53, TRIM, Jaw1, LTB, PTPRCAP

Breast cancer (BC) is the second leading cause of cancer death in women worldwide, and settings of specific prognostic factors and efficacious therapies are made difficult by phenotypic heterogeneity of BC subtypes. Therefore, there is a current urgent need to define novel predictive genetic predictors that may be useful for stratifying patients with distinct prognostic outcomes. Here, we looked for novel molecular signatures for triple negative breast cancers (TNBCs). By a bioinformatic approach, we identified a panel of genes, whose expression was positively correlated with disease-free survival in TNBC patients, namely IL18R1, CD53, TRIM, Jaw1, LTB, and PTPRCAP, showing specific immune expression profiles linked to survival prediction; most of these genes are indeed expressed in immune cells and are required for productive lymphocyte activation. According to our hypothesis, these genes were not, or poorly, expressed in different TNBC cell lines, derived from either primary breast tumours or metastatic pleural effusions. This conclusion was further supported in vivo, as immuno-histochemical analysis on biopsies of TNBC invasive ductal carcinomas highlighted differential expression of these six genes in cancer cells, as well as in intra- and peri-tumoral infiltrating lymphocytes. Our data open to the possibility that inter-tumour heterogeneity of immune markers might have predictive value; further investigations are recommended in order to establish the real power of cancer-related immune profiles as prognostic factors

Global mapping of cancers: The Cancer Genome Atlas and beyond

Cancer genomes have been explored from the early 2000s through massive exome sequencing efforts, leading to the publication of The Cancer Genome Atlas in 2013. Sequencing techniques have been developed alongside this project and have allowed scientists to bypass the limitation of costs for whole-genome sequencing (WGS) of single specimens by developing more accurate and extensive cancer sequencing projects, such as deep sequencing of whole genomes and transcriptomic analysis. The Pan-Cancer Analysis of Whole Genomes recently published WGS data from more than 2600 human cancers together with almost 1200 related transcriptomes. The application of WGS on a large database allowed, for the first time in history, a global analysis of features such as molecular signatures, large structural variations and noncoding regions of the genome, as well as the evaluation of RNA alterations in the absence of underlying DNA mutations. The vast amount of data generated still needs to be thoroughly deciphered, and the advent of machine-learning approaches will be the next step towards the generation of personalized approaches for cancer medicine. The present manuscript wants to give a broad perspective on some of the biological evidence derived from the largest sequencing attempts on human cancers so far, discussing advantages and limitations of this approach and its power in the era of machine learning

Free-amino acid metabolic profiling of visceral adipose tissue from obese subjects

Interest in adipose tissue pathophysiology and biochemistry have expanded considerably in the past two decades due to the ever increasing and alarming rates of global obesity and its critical outcome defined as metabolic syndrome (MS). This obesity-linked systemic dysfunction generates high risk factors of developing perilous diseases like type 2 diabetes, cardiovascular disease or cancer. Amino acids could play a crucial role in the pathophysiology of the MS onset. Focus of this study was to fully characterize amino acids metabolome modulations in visceral adipose tissues (VAT) from three adult cohorts: (i) obese patients (BMI 43-48) with metabolic syndrome (PO), (ii) obese subjects metabolically well (O), and (iii) non obese individuals (H). 128 metabolites identified as 20 protein amino acids, 85 related compounds and 13 dipeptides were measured by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography-/mass spectrometry GC/MS, in visceral fat samples from a total of 53 patients. Our analysis indicates a probable enhanced BCAA (leucine, isoleucine, valine) degradation in both VAT from O and PO subjects, while levels of their oxidation products are increased. Also PO and O VAT samples were characterized by: elevated levels of kynurenine, a catabolic product of tryptophan and precursor of diabetogenic substances, a significant increase of cysteine sulfinic acid levels, a decrease of 1-methylhistidine, and an up regulating trend of 3-methylhistidine levels. We hope this profiling can aid in novel clinical strategies development against the progression from obesity to metabolic syndrome

Biosynthesis and Cellular Functions of Tartaric Acid in Grapevines

Tartaric acid (TA) is an obscure end point to the catabolism of ascorbic acid (Asc). Here, it is proposed as a “specialized primary metabolite”, originating from carbohydrate metabolism but with restricted distribution within the plant kingdom and lack of known function in primary metabolic pathways. Grapes fall into the list of high TA-accumulators, with biosynthesis occurring in both leaf and berry. Very little is known of the TA biosynthetic pathway enzymes in any plant species, although recently some progress has been made in this space. New technologies in grapevine research such as the development of global co-expression network analysis tools and genome-wide association studies, should enable more rapid progress. There is also a lack of information regarding roles for this organic acid in plant metabolism. Therefore this review aims to briefly summarize current knowledge about the key intermediates and enzymes of TA biosynthesis in grapes and the regulation of its precursor, ascorbate, followed by speculative discussion around the potential roles of TA based on current knowledge of Asc metabolism, TA biosynthetic enzymes and other aspects of fruit metabolism

Free-amino acid metabolic profiling of visceral adipose tissue from obese subjects

Interest in adipose tissue pathophysiology and biochemistry have expanded considerably in the past two decades due to the ever increasing and alarming rates of global obesity and its critical outcome defined as metabolic syndrome (MS). This obesity-linked systemic dysfunction generates high risk factors of developing perilous diseases like type 2 diabetes, cardiovascular disease or cancer. Amino acids could play a crucial role in the pathophysiology of the MS onset. Focus of this study was to fully characterize amino acids metabolome modulations in visceral adipose tissues (VAT) from three adult cohorts: (i) obese patients (BMI 43-48) with metabolic syndrome (PO), (ii) obese subjects metabolically well (O), and (iii) non obese individuals (H). 128 metabolites identified as 20 protein amino acids, 85 related compounds and 13 dipeptides were measured by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) and gas chromatography-/mass spectrometry GC/MS, in visceral fat samples from a total of 53 patients. Our analysis indicates a probable enhanced BCAA (leucine, isoleucine, valine) degradation in both VAT from O and PO subjects, while levels of their oxidation products are increased. Also PO and O VAT samples were characterized by: elevated levels of kynurenine, a catabolic product of tryptophan and precursor of diabetogenic substances, a significant increase of cysteine sulfinic acid levels, a decrease of 1-methylhistidine, and an up regulating trend of 3-methylhistidine levels. We hope this profiling can aid in novel clinical strategies development against the progression from obesity to metabolic syndrome

Genome sequence of the Ornithopus/Lupinus-nodulating Bradyrhizobium sp. strain WSM471

Bradyrhizobium sp. strain WSM471 is an aerobic, motile, Gram-negative, non-spore-forming rod that was isolated from an effective nitrogen-(N-2) fixing root nodule formed on the annual legume Ornithopus pinnatus (Miller) Druce growing at Oyster Harbour, Albany district, Western Australia in 1982. This strain is in commercial production as an inoculant for Lupinus and Ornithopus. Here we describe the features of Bradyrhizobium sp. strain WSM471, together with genome sequence information and annotation. The 7,784,016 bp high-quality-draft genome is arranged in 1 scaffold of 2 contigs, contains 7,372 protein-coding genes and 58 RNA-only encoding genes, and is one of 20 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Community Sequencing Program