Giorgio Milazzo

Bio: Giorgio Milazzo is an academic researcher from University of Bologna. The author has contributed to research in topics: Neuroblastoma & Gene expression. The author has an hindex of 13, co-authored 25 publications receiving 2317 citations.

Growth of Rhodococcus sp. strain BCP1 on gaseous n-alkanes: new metabolic insights and transcriptional analysis of two soluble di-iron monooxygenase genes.

Abstract: Rhodococcus sp. strain BCP1 was initially isolated for its ability to grow on gaseous n-alkanes, which act as inducers for the co-metabolic degradation of low-chlorinated compounds. Here, both molecular and metabolic features of BCP1 cells grown on gaseous and short-chain n-alkanes (up to n-heptane) were examined in detail. We show that propane metabolism generated terminal and sub-terminal oxidation products such as 1- and 2-propanol, whereas 1-butanol was the only terminal oxidation product detected from butane metabolism. Two gene clusters, prmABCD and smoABCD – coding for soluble di-iron monooxgenases (SDIMOs) involved in gaseous n-alkanes oxidation – were detected in the BCP1 genome. By means of reverse transcriptase-quantitative PCR (RT-qPCR) analysis, a set of substrates inducing the expression of the sdimo genes in BCP1 were assessed as well as their transcriptional repression in the presence of sugars, organic acids or during the cell growth on rich medium (Luria Bertani broth). The transcriptional start sites of both the sdimo gene clusters were identified by means of primer extension experiments. Finally, proteomic studies revealed changes in the protein pattern induced by growth on gaseous- (n-butane) and/or liquid (n-hexane) short-chain n-alkanes as compared to growth on succinate. Among the differently expressed protein spots, two chaperonins and an isocytrate lyase were identified along with oxidoreductases involved in oxidation reactions downstream of the initial monooxygenase reaction step.

Histone deacetylases (HDACs): Evolution, specificity, role in transcriptional complexes, and pharmacological actionability

Abstract: Histone deacetylases (HDACs) are evolutionary conserved enzymes which operate by removing acetyl groups from histones and other protein regulatory factors, with functional consequences on chromatin remodeling and gene expression profiles. We provide here a review on the recent knowledge accrued on the zinc-dependent HDAC protein family across different species, tissues, and human pathologies, specifically focusing on the role of HDAC inhibitors as anti-cancer agents. We will investigate the chemical specificity of different HDACs and discuss their role in the human interactome as members of chromatin-binding and regulatory complexes.

Effects of a Novel Long Noncoding RNA, lncUSMycN, on N-Myc Expression and Neuroblastoma Progression

Abstract: BACKGROUND Patients with neuroblastoma due to the amplification of a 130-kb genomic DNA region containing the MYCN oncogene have poor prognoses METHODS Bioinformatics data were used to discover a novel long noncoding RNA, lncUSMycN, at the 130-kb amplicon RNA-protein pull-down assays were used to identify proteins bound to lncUSMycN RNA Kaplan-Meier survival analysis, multivariable Cox regression, and two-sided log-rank test were used to examine the prognostic value of lncUSMycN and NonO expression in three cohorts of neuroblastoma patients (n = 47, 88, and 476, respectively) Neuroblastoma-bearing mice were treated with antisense oligonucleotides targeting lncUSMycN (n = 12) or mismatch sequence (n = 13), and results were analyzed by multiple comparison two-way analysis of variance All statistical tests were two-sided RESULTS Bioinformatics data predicted lncUSMycN gene and RNA, and reverse-transcription polymerase chain reaction confirmed its three exons and two introns The lncUSMycN gene was coamplified with MYCN in 88 of 341 human neuroblastoma tissues lncUSMycN RNA bound to the RNA-binding protein NonO, leading to N-Myc RNA upregulation and neuroblastoma cell proliferation High levels of lncUSMycN and NonO expression in human neuroblastoma tissues independently predicted poor patient prognoses (lncUSMycN: hazard ratio [HR] = 187, 95% confidence interval [CI] = 106 to 328, P = 03; NonO: HR = 248, 95% CI = 134 to 457, P = 004) Treatment with antisense oligonucleotides targeting lncUSMycN in neuroblastoma-bearing mice statistically significantly hindered tumor progression (P < 001) CONCLUSIONS Our data demonstrate the important roles of lncUSMycN and NonO in regulating N-Myc expression and neuroblastoma oncogenesis and provide the first evidence that amplification of long noncoding RNA genes can contribute to tumorigenesis

Aerobic Growth of Rhodococcus aetherivorans BCP1 Using Selected Naphthenic Acids as the Sole Carbon and Energy Sources

Abstract: Naphthenic acids (NAs) are an important group of toxic organic compounds naturally occurring in hydrocarbon deposits. This work shows that Rhodococcus aetherivorans BCP1 cells not only utilize a mixture of eight different NAs (8XNAs) for growth but they are also capable of marked degradation of two model NAs, cyclohexanecarboxylic acid (CHCA) and cyclopentanecarboxylic acid (CPCA) when supplied at concentrations from 50 to 500 mgL-1. The growth curves of BCP1 on 8XNAs, CHCA, and CPCA showed an initial lag phase not present in growth on glucose, which presumably was related to the toxic effects of NAs on the cell membrane permeability. BCP1 cell adaptation responses that allowed survival on NAs included changes in cell morphology, production of intracellular bodies and changes in fatty acid composition. Transmission electron microscopy (TEM) analysis of BCP1 cells grown on CHCA or CPCA showed a slight reduction in the cell size, the production of EPS-like material and intracellular electron-transparent and electron-dense inclusion bodies. The electron-transparent inclusions increased in the amount and size in NA-grown BCP1 cells under nitrogen limiting conditions and contained storage lipids as suggested by cell staining with the lipophilic Nile Blue A dye. Lipidomic analyses revealed significant changes with increases of methyl-branched (MBFA) and polyunsaturated fatty acids (PUFA) examining the fatty acid composition of NAs-growing BCP1 cells. PUFA biosynthesis is not usual in bacteria and, together with MBFA, can influence structural and functional processes with resulting effects on cell vitality. Finally, through the use of RT (Reverse Transcription)-qPCR, a gene cluster (chcpca) was found to be transcriptionally induced during the growth on CHCA and CPCA. Based on the expression and bioinformatics results, the predicted products of the chcpca gene cluster are proposed to be involved in aerobic NA degradation in R. aetherivorans BCP1. This study provides first insights into the genetic and metabolic mechanisms allowing a Rhodococcus strain to aerobically degrade NAs.

Inhibition of polyamine synthesis and uptake reduces tumor progression and prolongs survival in mouse models of neuroblastoma

Abstract: Amplification of the MYCN oncogene is associated with an aggressive phenotype and poor outcome in childhood neuroblastoma. Polyamines are highly regulated essential cations that are frequently elevated in cancer cells, and the rate-limiting enzyme in polyamine synthesis, ornithine decarboxylase 1 (ODC1), is a direct transcriptional target of MYCN. Treatment of neuroblastoma cells with the ODC1 inhibitor difluoromethylornithine (DFMO), although a promising therapeutic strategy, is only partially effective at impeding neuroblastoma cell growth due to activation of compensatory mechanisms resulting in increased polyamine uptake from the surrounding microenvironment. In this study, we identified solute carrier family 3 member 2 (SLC3A2) as the key transporter involved in polyamine uptake in neuroblastoma. Knockdown of SLC3A2 in neuroblastoma cells reduced the uptake of the radiolabeled polyamine spermidine, and DFMO treatment increased SLC3A2 protein. In addition, MYCN directly increased polyamine synthesis and promoted neuroblastoma cell proliferation by regulating SLC3A2 and other regulatory components of the polyamine pathway. Inhibiting polyamine uptake with the small-molecule drug AMXT 1501, in combination with DFMO, prevented or delayed tumor development in neuroblastoma-prone mice and extended survival in rodent models of established tumors. Our findings suggest that combining AMXT 1501 and DFMO with standard chemotherapy might be an effective strategy for treating neuroblastoma.

Efficient techniques for the removal of toxic heavy metals from aquatic environment: A review

Abstract: The controversy related to the environment pollution is increasing in human life and in the eco-system. Especially, the water pollution is growing rapidly due to the wastewater discharge from the industries. The only way to find the new water resource is the reuse of treated wastewater. Several remediation technologies are available which provides a convenience to reuse the reclaimed wastewater. Heavy metals like Zn, Cu, Pb, Ni, Cd, Hg, etc. contributes various environmental problems based on their toxicity. These toxic metals are exposed to human and environment, the accumulation of ions takes place which causes serious health and environmental hazards. Hence, it is a major concern in the environment. Due to this concern, the significance of developing technology for removing heavy metals has been increased. This paper contributes the outline of new literature with two objectives. First, it provides the sketch about treatment technologies followed by their heavy metal capture capacity from industrial effluent. The treatment performance, their remediation capacity and probable environmental and health impacts were deliberated in this review article. Conclusively, this review paper furnishes the information about the important methods incorporated in lab scale studies which are required to identify the feasible and convenient wastewater treatment. Moreover, attempts have been made to confer the emphasis on sequestration of heavy metals from industrial effluent and establish the scientific background for reducing the discharge of heavy metals into the environment.

Trade-offs between multifunctionality and profit in tropical smallholder landscapes

Abstract: Land-use transitions can enhance the livelihoods of smallholder farmers but potential economic-ecological trade-offs remain poorly understood. Here, we present an interdisciplinary study of the environmental, social and economic consequences of land-use transitions in a tropical smallholder landscape on Sumatra, Indonesia. We find widespread biodiversity-profit trade-offs resulting from land-use transitions from forest and agroforestry systems to rubber and oil palm monocultures, for 26,894 aboveground and belowground species and whole-ecosystem multidiversity. Despite variation between ecosystem functions, profit gains come at the expense of ecosystem multifunctionality, indicating far-reaching ecosystem deterioration. We identify landscape compositions that can mitigate trade-offs under optimal land-use allocation but also show that intensive monocultures always lead to higher profits. These findings suggest that, to reduce losses in biodiversity and ecosystem functioning, changes in economic incentive structures through well-designed policies are urgently needed.

RNA in cancer.

Abstract: While the processing of mRNA is essential for gene expression, recent findings have highlighted that RNA processing is systematically altered in cancer. Mutations in RNA splicing factor genes and the shortening of 3' untranslated regions are widely observed. Moreover, evidence is accumulating that other types of RNAs, including circular RNAs, can contribute to tumorigenesis. In this Review, we highlight how altered processing or activity of coding and non-coding RNAs contributes to cancer. We introduce the regulation of gene expression by coding and non-coding RNA and discuss both established roles (microRNAs and long non-coding RNAs) and emerging roles (selective mRNA processing and circular RNAs) for RNAs, highlighting the potential mechanisms by which these RNA subtypes contribute to cancer. The widespread alteration of coding and non-coding RNA demonstrates that altered RNA biogenesis contributes to multiple hallmarks of cancer.