Primo Bilancio di Genere dell'Ateneo Fridericiano

YesThe first annual report on Gender at the Federico II University.FP

指冷丝弦吟怨曲，声翻经典响新雷——评弹《雷雨》的艺术魅力与文化价值

LIBO is a proton accelerator that operates at 3 GHz, the same frequency as the one adopted in the about 7500 electron linacs used for radiotherapy all over the world. Such a high frequency was chosen to obtain a large gradient (on average more than 10 MV/m), and thus a short linac (about 15 m) to boost the energy of the protons, extracted at about 60 MeV from a cyclotron, up to the 200 MeV needed for the treatment of deep-seated tumours. This paper describes the design study of the full 3 GHz Side Coupled Linac (modular structure, nine modules) and the construction and tests of the LIBO prototype (first module), which was built to accelerate protons from 62 to 74 MeV with an RF peak power of 4.4 MW. The items discussed are the beam dynamics parameters of the module (longitudinal and transverse acceptances), the constructional elements and procedures, the accuracies of the various mechanical elements, the cooling system, the RF tuning, the RF measurement and the RF power tests. These tests showed that, after a short conditioning time, the gradient in each of the four tanks of the module could reach 28.5 MV/m, much larger than the nominal project value (15.8 MV/m). The last section of the paper describes the successful acceleration tests performed at the Laboratori Nazionali del Sud of INFN in Catania with a solid-state 3 GHz modulator lent by IBA

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Cloning and sequencing of the gene encoding thermostable elongation factor 2 in Sulfolobus solfataricus

The gene (aEF-2) coding for the translation elongation factor 2 (aEF-2) in the thermoacidophilic archaebacterium, Sulfolobus solfataricus, has been cloned and sequenced. The deduced primary structure of aEF-2 is composed of 735 amino acids (aa), excluding the Met start residue. There are no Cys residues and the calculated M(r) is 81,699. In the coding region of aEF-2, the high A + T content greatly influences the codon usage. From the alignment of the primary structure of aEF-2 with that of the analogous factors from the three kingdoms, aa identities were derived. The greatest identity (82%) was found with EF-2 from Sulfolobus acidocaldarius; lower values were observed with other archaebacterial EF-2 (45-47%), eukaryotic EF-2 (38-40%) and with the functional eubacterial analogue EF-G (28-31%). aEF-2 possesses the consensus sequences required for a GTP-binding protein and the four regions which are supposed to be involved in the functional regulation of EF-2/EF-G. These data should have phylogenetic implications

Enzymes involved in the oxidative stress in Sulfolobus solfataricus.

The present article summarises our recent work carried out on enzymes involved in the oxidative stress in the hyperthermophilic archaeon Sulfolobus solfataricus. The functional role of three key enzymes, superoxide dismutase (SOD), thioredoxin reductase (TrxR), and NADH oxidase (NOX) has been investigated. The study included a detailed structure–function relationship on these ubiquitous proteins through the characterisation of their molecular and functional properties, the comparison with the features of the corresponding enzymes isolated from taxonomically different sources, and a mutagenic analysis on some specific amino acid residues. S. solfataricus SOD belongs to the family of Fe- and Mn- SOD and possesses a very compact homotetrameric structure, responsible for its great heat resistance. The mutagenic analysis regarded two interacting residues of the active site, namely a conserved tyrosine and a semi–invariant histidine. The data on the tyrosine residue point to its relevance in the catalytic mechanism of superoxide dismutation, and indicate its high reactivity towards modifying agents; vice versa, the histidine residue is important for the structural architecture of the active site. S. solfataricus TrxR, an enzyme previously isolated for its ability to oxidise NADH, belongs to the family of class II pyridine nucleotide–disulphide oxidoreductases. It possesses two cysteine residues in the active site, forming a disulphide bridge essential for both reductase and NADH oxidase activities, a finding supported also by mutagenic analysis. Furthermore, inhibition studies indicate that S. solfataricus TrxR, structurally similar to eubacterial counterparts, is functionally closer to eukaryal TrxR. S. solfataricus NOX is a homodimeric flavo-enzyme able to oxidise both NADH and NADPH, and belongs to the NOX family forming H2O2 as end product of the reaction. The lack of cysteines in its primary structure indicates that the electron transfer from NAD(P)H to molecular oxygen does not involve a disulphide bridge. The results of this investigation indicate that Sulfolobus solfataricus possesses efficient enzyme systems for the protection against oxidative stress. In particular, SOD and TrxR from this archaeal source share similar functional and molecular properties with their mitochondrial counterparts, thus supporting the hypothesis that the Sulfolobus genus is the putative ancestor of animal mitochondria. Vice versa, the properties of S. solfataricus NOX confirm that this enzyme belongs to a protein family scarcely conserved during evolution; the data also suggest a possible involvement of this enzyme in the protection against oxygen toxicity

Enzymes involved in the oxidative stress in Sulfolobus solfataricus

The present article summarises our recent work carried out on enzymes involved in the oxidative stress in the hyperthermophilic archaeon Sulfolobus solfataricus. The functional role of three key enzymes, superoxide dismutase (SOD), thioredoxin reductase (TrxR), and NADH oxidase (NOX) has been investigated. The study included a detailed structure–function relationship on these ubiquitous proteins through the characterisation of their molecular and functional properties, the comparison with the features of the corresponding enzymes isolated from taxonomically different sources, and a mutagenic analysis on some specific amino acid residues. S. solfataricus SOD belongs to the family of Fe- and Mn-SOD and possesses a very compact homotetrameric structure, responsible for its great heat resistance. The mutagenic analysis regarded two interacting residues of the active site, namely a conserved tyrosine and a semi–invariant histidine. The data on the tyrosine residue point to its relevance in the catalytic mechanism of superoxide dismutation, and indicate its high reactivity towards modifying agents; vice versa, the histidine residue is important for the structural architecture of the active site. S. solfataricus TrxR, an enzyme previously isolated for its ability to oxidise NADH, belongs to the family of class II pyridine nucleotide–disulphide oxidoreductases. It possesses two cysteine residues in the active site, forming a disulphide bridge essential for both reductase and NADH oxidase activities, a finding supported also by mutagenic analysis. Furthermore, inhibition studies indicate that S. solfataricus TrxR, structurally similar to eubacterial counterparts, is functionally closer to eukaryal TrxR. S. solfataricus NOX is a homodimeric flavo-enzyme able to oxidise both NADH and NADPH, and belongs to the NOX family forming H2O2 as end product of the reaction. The lack of cysteines in its primary structure indicates that the electron transfer from NAD(P)H to molecular oxygen does not involve a disulphide bridge. The results of this investigation indicate that Sulfolobus solfataricus possesses efficient enzyme systems for the protection against oxidative stress. In particular, SOD and TrxR from this archaeal source share similar functional and molecular properties with their mitochondrial counterparts, thus supporting the hypothesis that the Sulfolobus genus is the putative ancestor of animal mitochondria. Vice versa, the properties of S. solfataricus NOX confirm that this enzyme belongs to a protein family scarcely conserved during evolution; the data also suggest a possible involvement of this enzyme in the protection against oxygen toxicity