Il prologo della Assis Distributio e l’inizio della carriera di Volusio Meciano

A good analysis of the Prologue shows that the author, the jurist Valerius Maecianus, wrote this treatise just after the year 139 AD, in order to give to the young Marcus Aurelius didactic information about the assis distributio (the division of money and weight). Of this matter he presents rhetorically the importance and distinguishes parts, terminology, characters

Natural risk assessment and decision planning for disaster mitigation

International audienceIn this paper, decisional models are introduced aiming at defining a general framework for natural disaster mitigation. More specifically, an integrated approach based on system modelling and optimal resource assignment is presented in order to support the decision makers in pre-operational and real-time management of forest fire emergencies. Some strategies for pre-operative and real time risk management will be described and formalized as optimal resource assignment problems. To this end, some models capable to describe the resources dynamics will be introduced, both in pre-operative phase and in real-time phase

Inhibition of acetylpolyamine and spermine oxidases by the polyamine analogue chlorhexidine

""Acetylpolyamine and spermine oxidases are involved in the catabolism of polyamines. The discovery of selective. inhibitors of these enzymes represents an important tool for the development of novel anti-neoplastic drugs. Here, a. comparative study on acetylpolyamine and spermine oxidases inhibition by the polyamine analogue chlorhexidine. is reported. Chlorhexidine is an antiseptic diamide, commonly used as a bactericidal and bacteriostatic agent.. Docking simulations indicate that chlorhexidine binding to these enzymes is compatible with the stereochemical. properties of both acetylpolyamine oxidase and spermine oxidase active sites. In fact, chlorhexidine is predicted. to establish several polar and hydrophobic interactions with the active site residues of both enzymes, with binding. energy values ranging from −7.6 to −10.6 kcal\\\/mol. In agreement with this hypothesis, inhibition studies indicate that. chlorhexidine behaves as a strong competitive inhibitor of both enzymes, values of Ki being 0.10 μM and 0.55 μM for. acetylpolyamine oxidase and spermine oxidase, respectively."

Conversion of cytochrome c into a peroxidase: inhibitory mechanisms and implication for neurodegenerative diseases.

A further function of cytochrome c (cyt c), beyond respiration, is realized outside mitochondria in the apoptotic program. In the early events of apoptosis, the interaction of cyt c with a mitochondrion-specific phospholipid, cardiolipin (CL), brings about a conformational transition of the protein and acquirement of peroxidase activity. The hallmark of cyt c with peroxidase activity is its partial unfolding accompanied by loosening of the Fe sixth axial bond and an enhanced access of the heme catalytic site to small molecules like H2O2. To investigate the peroxidase activity of non-native cyt c, different forms of the protein were analyzed with the aim to correlate their structural features with the acquired enzymatic activity and apoptogenic properties (wt cyt c/CL complex and two single cyt c variants, H26Y and Y67H, free and bound to CL). The results suggest that cyt c may respond to different environments by changing its fold thus favouring the exertion of different biological functions in different pathophysiological cell conditions. Transitions among different conformations are regulated by endogenous molecules such as ATP and may be affected by synthetic molecules such as minocycline, thus suggesting a mechanism explaining its use as therapeutic agent impacting on disease-associated oxidative and apoptotic mechanisms

The 40s Omega-loop plays a critical role in the stability and the alkaline conformational transition of cytochrome c

The structural and redox properties of a non-covalent complex reconstituted upon mixing two non-contiguous fragments of horse cytochrome c, the residues 1 - 38 heme-containing N-fragment with the residues 57 - 104 C-fragment, have been investigated. With respect to native cyt c, the complex lacks a segment of 18 residues, corresponding, in the native protein, to an omega ( W)loop region. The fragment complex shows compact structure, native-like alpha-helix content but a less rigid atomic packing and reduced stability with respect to the native protein. Structural heterogeneity is observed at pH 7.0, involving formation of an axially misligated low-spin species and consequent partial displacement of Met80 from the sixth coordination position of the heme-iron. Spectroscopic data suggest that a lysine ( located in the Met80-containing loop, namely Lys72, Lys73, or Lys79) replaces the methionine residue. The residues 1 - 38/57 - 104 fragment complex shows an unusual biphasic alkaline titration characterized by a low (pK(a1)= 6.72) and a high pK(a)-associated state transition (pK(a2)= 8.56); this behavior differs from that of native cyt c, which shows a monophasic alkaline transition ( pK(a)= 8.9). The data indicate that the 40s Omega-loop plays an important role in the stability of cyt c and in ensuring a correct alkaline conformational transition of the protein

The key role played by charge in the interaction of cytochrome c with cardiolipin

Cytochrome c undergoes structural variations upon binding of cardiolipin, one of the phospholipids constituting the mitochondrial membrane. Although several mechanisms governing cytochrome c/cardiolipin (cyt c/CL) recognition have been proposed, the interpretation of the process remains, at least in part, unknown. To better define the steps characterizing the cyt c-CL interaction, the role of Lys72 and Lys73, two residues thought to be important in the protein/lipid binding interaction, were recently investigated by mutagenesis. The substitution of the two (positively charged) Lys residues with Asn revealed that such mutations cancel the CL-dependent peroxidase activity of cyt c; furthermore, CL does not interact with the Lys72Asn mutant. In the present paper, we extend our study to the Lys → Arg mutants to investigate the influence exerted by the charge possessed by the residues located at positions 72 and 73 on the cyt c/CL interaction. On the basis of the present work a number of overall conclusions can be drawn: (i) position 72 must be occupied by a positively charged residue to assure cyt c/CL recognition; (ii) the Arg residues located at positions 72 and 73 permit cyt c to react with CL; (iii) the replacement of Lys72 with Arg weakens the second (low-affinity) binding transition; (iv) the Lys73Arg mutation strongly increases the peroxidase activity of the CL-bound protein

Role of lysines in cytochrome c – cardiolipin interaction

Cytochrome c undergoes structural variations during the apoptotic process; such changes have been related with modifications occurring in the protein when it forms a complex with cardiolipin, one of the phospholipids constituting the mitochondrial membrane. Although several studies have been performed to identify the site(s) of the protein involved in the cytochrome c/cardiolipin interaction, to date the location of this hosting region(s) remains unidentified and is a matter of debate. To gain a deeper insight into the reaction mechanism, we investigate the role that the Lys72, Lys73 and Lys79 residues play in the cytochrome c/cardiolipin interaction, as these side chains appear to be critical for cytochrome c/cardiolipin recognition. The Lys72Asn, Lys73Asn, Lys79Asn, Lys72/73Asn and Lys72/73/79Asn mutants of horse heart cytochrome c were produced and characterized by circular dichroism, UV-visible and resonance Raman spectroscopies, and the effects of the mutations on the interaction of the variants with cardiolipin have been investigated. The mutants are characterized by a subpopulation with non-native axial coordination, and are less stable than the wild type protein. Furthermore, the mutants lacking Lys72 and/or Lys79 do not bind cardiolipin and those lacking Lys73, although they form a complex with the phospholipid, do not show any peroxidase activity. These observations indicate that the Lys72, Lys73 and Lys79 residues stabilize the native axial Met80-Fe(III) coordination as well as the tertiary structure of cytochrome c. Moreover, while Lys72 and Lys79 are critical for cytochrome c/cardiolipin recognition, the simultaneous presence of Lys72, Lys73 and Lys79 is necessary for peroxidase activity of cardiolipin-bound cytochrome c

Multi-colour optical monitoring of eight red blazars

We present the observational results of multi-colour optical monitoring of eight red blazars from 2003 September to 2004 February. The aim of our monitoring is to investigate the spectral variability as well as the flux variations at short and long time scales. The observations were carried out using the 1.0 m robotic telescope of Mt. Lemmon Optical Astronomy Observatory, in Arizona, USA, the 0.6 m telescope of Sobaeksan Optical Astronomy Observatory and the 1.8 m telescope of Bohyunsan Optical Astronomy Observatory, in the Republic of Korea. During the observations, all sources show strong flux variations with amplitudes of larger than 0.5 mag. Variations with amplitudes of over 1 mag are found in four sources. Intraday variations with amplitudes larger than 0.15 mag, and a rapid brightness increase with a rate of ~0.2 mag per day in four days, are detected in S5 0716+71. We investigate the relationship between the colour index and source brightness for each source. We find that two out of three FSRQs tend to be redder when they are brighter, and, conversely, all BL Lac objects tend to be bluer. In particular, we find a significant anti-correlation between the V-I colour index and R magnitude for 3C 454.3. This implies that the spectrum became steeper when the source was brighter, which is opposite to the common trend for blazars. In contrast, significant positive correlations are found in 3C 66A, S5 0716+71, and BL Lac. However, there are only very weak correlations for PKS 0735+17 and OJ 287. We propose that the different relative contributions of the thermal versus non-thermal radiation to the optical emission may be responsible for the different trends of the colour index with brightness in FSRQs and BL Lac objects.Comment: 15 pages, 12 figures. Accepted for publication in A&