A perspective on DNA damage-induced potentiation of the pentose phosphate shunt and reductive stress in chemoresistance

Metabolic rearrangements and genome instability are two hallmarks of cancer. Recent evidence from our laboratory demonstrates that persistent DNA lesions hampering transcription may cause glucose rerouting through the pentose phosphate shunt and reductive stress. Here, we highlight the relevance of these findings for cancer and chemoresistance development

Ignition and reaction mechanism of Co-Al and Nb-Al intermetallic compounds prepared by combustion synthesis

The ignition and propagation mechanism of the self-propagating high-temperature synthesis of several cobalt and niobium aluminides was investigated. Two propagation mechanisms were identified depending on the stoichiometry of the starting mixture. Al-rich compositions propagate through a dissolution-precipitation mechanism while Al-poor mixtures require solid state diffusion. The ignition temperatures were measured by means of microthermocouples in quasi-adiabatic conditions through experiments carried out in thermal explosion mode. Ignition temperatures were found to be characteristic of each system and to depend strongly on reactants particle size. Ignition energies for all compositions were evaluated through a mathematical model

Cysteine oxidation and redox signaling in dopaminergic neurons physiology and in Parkinson's disease

Parkinson’s disease (PD) is a neurological disorder affecting dopaminergic neurons in the nigrostriatal pathways of the brain. PD is a multifactorial disease and its causes should be sought in detrimental interactions between genes and environment. Since early mechanistic studies, excessive oxidation – or oxidative stress – emerged as a recurring and fundamental pathogenic mechanism, and consequently received significant attention. More recent evidence obtained at single-cell resolution, however, indicates that dopaminergic neurons in the substantia nigra display increased oxidation levels also in normal, physiological conditions; differently than pathological oxidation, the importance of this phenomenon is underappreciated. The nigrostriatal dopaminergic system is involved in behavioral strategies that have been under strong evolutionary pressure. It is therefore improbable that physiological oxidation in dopamine neurons is accidental. Here, we review recent literature to argue that moderate oxidation improves redox signaling – which in dopamine neurons is intertwined with electrophysiological activity and is i

Solid state hydrogen storage in alanates and alanate-based compounds: a review

The safest way to store hydrogen is in solid form, physically entrapped in molecular form in highly porous materials, or chemically bound in atomic form in hydrides. Among the different families of these compounds, alkaline and alkaline earth metals alumino-hydrides (alanates) have been regarded as promising storing media and have been extensively studied since 1997, when Bogdanovic and Schwickardi reported that Ti-doped sodium alanate could be reversibly dehydrogenated under moderate conditions. In this review, the preparative methods; the crystal structure; the physico-chemical and hydrogen absorption-desorption properties of the alanates of Li, Na, K, Ca, Mg, Y, Eu, and Sr; and of some of the most interesting multi-cation alanates will be summarized and discussed. The most promising alanate-based reactive hydride composite (RHC) systems developed in the last few years will also be described and commented on concerning their hydrogen absorption and desorption performanc

Effect of the partial replacement of CaH2 with CaF2 in the Mixed System CaH2 + MgB2

In this work the effect of a partial replacement of CaH2 with CaF2 on the sorption properties of the system CaH2 + MgB2 has been studied. The first five hydrogen absorption and four desorption reactions of the CaH2 + MgB2 and 3CaH2 + CaF2 + 4MgB2 systems were investigated by means of volumetric measurements, high-pressure differential scanning calorimetric technique (HP-DSC), 11B and 19F MAS NMR spectroscopy, and in situ synchrotron radiation powder X-ray diffraction (SR-PXD). It was observed that already during the mixing of the reactants formation of a nonstoichiometric CaF2-xHx solid solution takes place. Formation of the CaF2-xHx solid solution sensibly affects the overall hydrogen sorption reactions of the system CaH2 + MgB2

NaAlH4 production from waste aluminum by reactive ball milling

Due to its thermodynamic properties and high reversibility, Ti doped sodium alanateis considered as a prototype hydrogen storage material. In this work we show how sodium alanate can be synthesized by reactive ball milling using aluminum particles obtained from recycled waste incineration slag. The synthesis was monitoredwith an in situ milling vial and characterized stepwise by PXD and DTA analyses. The sorption properties of the material were investigated using in situ synchrotron radiation PXD and volumetric analyses. A complete conversion of the starting reactants was obtained

Activation of the DNA damage response in vivo in synucleinopathy models of Parkinson\xe2\x80\x99s disease

The involvement of DNA damage and repair in aging processes is well established. Aging is an unequivocal risk factor for chronic neurodegenerative diseases, underscoring the relevance of investigations into the role that DNA alterations may have in the pathogenesis of these diseases. Consistently, even moderate impairment of DNA repair systems facilitates the onset of pathological features typical of PD that include derangement of the dopaminergic system, mitochondrial dysfunction, and alpha-synuclein stress. The latter establishes a connection between reduced DNA repair capacity and a cardinal feature of PD, alpha-synuclein pathology. It remains to be determined, however, whether alpha-synuclein stress activates in vivo the canonical signaling cascade associated with DNA damage, which is centered on the kinase ATM and substrates such as \xce\xb3H2Ax and 53BP1. Addressing these issues would shed light on age-related mechanisms impinging upon PD pathogenesis and neurodegeneration in particular. We analyzed two different synucleinopathy PD mouse models based either on intranigral delivery of AAV-expressing human alpha-synuclein, or intrastriatal injection of human alpha-synuclein pre-formed fibrils. In both cases, we detected a significant increase in \xce\xb3H2AX and 53BP1 foci, and in phospho-ATM immunoreactivity in dopaminergic neurons, which collectively indicate DNA damage and activation of the DNA damage response. Mechanistic experiments in cell cultures indicate that activation of the DNA damage response is caused, at least in part, by pro-oxidant species because it is prevented by exogenous or endogenous antioxidants, which also rescue mitochondrial anomalies caused by proteotoxic alpha-synuclein. These in vivo and in vitro findings reveal that the cellular stress mediated by alpha-synuclein\xe2\x80\x94a pathological hallmark in PD\xe2\x80\x94elicits DNA damage and activates the DNA damage response. The toxic cascade leading to DNA damage involves oxidant stress and mitochondrial dysfunction The data underscore the importance of DNA quality control for preservation of neuronal integrity and protection against neurodegenerative processes

Hydrogen storage systems from waste Mg alloys

The production cost of materials for hydrogen storage is one of the major issues to be addressed in order to consider them suitable for large scale applications. In the last decades several authors reported on the hydrogen sorption properties of Mg and Mg-based systems. In this work magnesium industrial wastes of AZ91 alloy and Mg-10 wt.% Gd alloy are used for the production of hydrogen storage materials. The hydrogen sorption properties of the alloys were investigated by means of volumetric technique, in situ synchrotron radiation powder X-ray diffraction (SR-PXD) and calorimetric methods. The measured reversible hydrogen storage capacity for the alloys AZ91 and Mg-10 wt.% Gd are 4.2 and 5.8 wt.%, respectively. For the Mg-10 wt.% Gd alloy, the hydrogenated product was also successfully used as starting reactant for the synthesis of Mg(NH2)2 and as MgH2 substitute in the Reactive Hydride Composite (RHC) 2LiBH4 + MgH 2. The results of this work demonstrate the concrete possibility to use Mg alloy wastes for hydrogen storage purposes

Bioenergetics in fibroblasts of patients with Huntington disease are associated with age at onset

Objective We aimed to assess whether differences in energy metabolism in fibroblast cell lines derived from patients with Huntington disease were associated with age at onset independent of the cytosine-adenine-guanine (CAG) repeat number in the mutant allele. Methods For this study, we selected 9 pairs of patients with Huntington disease matched for mutant CAG repeat size and sex, but with a difference of at least 10 years in age at onset, using the Leiden Huntington disease database. From skin biopsies, we isolated fibroblasts in which we (1) quantified the ATP concentration before and after a hydrogen-peroxide challenge and (2) measured mitochondrial respiration and glycolysis in real time, using the Seahorse XF Extracellular Flux Analyzer XF24. Results The ATP concentration in fibroblasts was significantly lower in patients with Huntington disease with an earlier age at onset, independent of calendar age and disease duration. Maximal respiration, spare capacity, and respiration dependent on complex II activity, and indices of mitochondrial respiration were significantly lower in patients with Huntington disease with an earlier age at onset, again independent of calendar age and disease duration. Conclusions A less efficient bioenergetics profile was found in fibroblast cells from patients with Huntington disease with an earlier age at onset independent of mutant CAG repeat size. Thus, differences in bioenergetics could explain part of the residual variation in age at onset in Huntington disease