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La nuova Lista Rossa della flora Italiana comprende tutte le "policy" specie italiane e altre specie di nota conservazione e comprende 400 taxa di cui il 65% sono minacciate di estinzione. La Lista Rossa si basa su un enorme data-set georeferenziato utile per gli scopi di conservazione. - The New Red List of the Italian Flora includes all the Italian policy species and other species of known conservation concerns for a total of 400 taxa, 65% of which are threatened with extinction. The Red List is based on a huge georeferenced data-set useful for conservation purposes.

The effect of geographical isolation on the inter- and intra-specific seed variability of the Astragalus tragacantha complex was investigated by using a computer-aided imaging system. In particular, seed morphometric and colorimetric features of Astragalus balearicus , A. tegulensis , A. terraccianoi , A. thermensis and A. tragacantha were measured and the data were used to discriminate among regions of provenance, taxa and populations. Discriminant analysis of the data supports the accepted taxonomy of the group and the hypothesis that interspecific differentiation resulted from geographical isolation. The results also showed a positive correlation between the wideness of species’ distribution and the levels of seed intra-specific variability.

Background and Aims The Mediterranean Basin is one of the most important regions for the Earths plant biodiversity; however, the scarcity of studies on fine scale patterns of genetic variation in this region is striking. Here, an assessment is made of the spatial genetic structure of all known locations of the three Sardinian endemic species of Aquilegia in order to determine the relative roles of gene flow and genetic drift as underlying evolutionary forces canalizing the divergence of Sardinian Aquilegia taxa, and to see if the spatial genetic structure found fits the current taxonomic differentiation of these taxa. Methods DNA from 89 individuals from all known locations of Aquilegia across Sardinia was analysed by means of amplified fragment length polymorphism (AFLP) markers. Both principal co-ordinates analysis (PCoA) and Bayesian clustering analyses were used to determine the spatial genetic structure irrespective of any taxonomic affiliation. Historical effects of gene flow and genetic drift were assessed by checking for the existence of isolation-by-distance patterns. Key Results STRUCTURE and PCoA analyses revealed a pattern of genetic variation geographically structured into four spatial genetic groups. No migrationdrift equilibrium was detected for Aquilegia in Sardinia, when analysed either as a whole or in individual groups. The scenario approached a Case III pattern sensu Hutchinson and Templeton, which is associated with extreme isolation conditions where genetic drift has historically played a dominant role over gene flow. Conclusions The pattern of genetic variation of Sardinian taxa of Aquilegia indicates that genetic drift has been historically more influential than gene flow on population structure of Sardinian species of Aquilegia. Limited seed dispersal and divergent selection imposed by habitat conditions have been probably the main causes reinforcing post-Pleistocene geographical isolation of Aquilegia populations. The spatial genetic structure found here is not fully compatible with current taxonomic affiliations of Sardinian Aquilegia taxa. This is probably a consequence of the uncoupling between morphological and genetic patterns of differentiation frequently found in recently radiated taxa. © The Author 2012.

Vitamin D response elements (VDREs) have been found in the promoter region of the MS-associated allele HLA-DRB1*15:01, suggesting that with low vitamin D availability VDREs are incapable of inducing *15:01 expression allowing in early life autoreactive T-cells to escape central thymic deletion. The Italian island of Sardinia exhibits a very high frequency of MS and high solar radiation exposure. We test the contribution of VDREs analysing the promoter region of the MS-associated DRB1 *04:05, *03:01, *13:01 and *15:01 and non-MS-associated *16:01, *01, *11, *07:01 alleles in a cohort of Sardinians (44 MS patients and 112 healthy subjects). Sequencing of the DRB1 promoter region revealed a homozygous canonical VDRE in all *15:01, *16:01, *11 and in 45/73 *03:01 and in heterozygous state in 28/73 *03:01 and all *01 alleles. A new mutated homozygous VDRE was found in all *13:03, *04:05 and *07:01 alleles. Functionality of mutated and canonical VDREs was assessed for its potential to modulate levels of DRB1 gene expression using an in vitro transactivation assay after stimulation with active vitamin D metabolite. Vitamin D failed to increase promoter activity of the *04:05 and *03:01 alleles carrying the new mutated VDRE, while the *16:01 and *03:01 alleles carrying the canonical VDRE sequence showed significantly increased transcriptional activity. The ability of VDR to bind the mutant VDRE in the DRB1 promoter was evaluated by EMSA. Efficient binding of VDR to the VDRE sequence found in the *16:01 and in the *15:01 allele reduced electrophoretic mobility when either an anti-VDR or an anti-RXR monoclonal antibody was added. Conversely, the Sardinian mutated VDRE sample showed very low affinity for the RXR/VDR heterodimer. These data seem to exclude a role of VDREs in the promoter region of the DRB1 gene in susceptibility to MS carried by DRB1* alleles in Sardinian patients.

Background: Sardinia is a known high-risk area for multiple sclerosis (MS), but no data for south-western Sardinia (SWS) are available. SWS has a genetically homogeneous population, apart from St Peter Island, and represents a peculiar environment related to the industrial, mineralogical and military economy. Objective: To estimate prevalence and incidence and to evaluate temporal trends and geographical distribution of MS in SWS. Methods: MS prevalence was evaluated on 31 December 2007 and crude mean annual incidence rate was defined between 2003 and 2007. Temporal trend in MS incidence was assessed using the Armitage test. To identify MS clusters, Standard Morbidity Ratio (SMR) was calculated for each village and geographical distribution prevalence by means of a Bayesian hierarchical model. Results: Total crude prevalence rate was 210.4 (95% CI 186.3–234.5): 280.3 (95% CI 241.4–319.3) for females, 138 (95% CI 110.1–165.8) for males. The crude mean annual incidence rate was 9.7/100,000 (95% CI 3.4–13.2): 4.7/100,000 (95% CI 2.4–17.0) and 14.6/100,000 (95% CI 11.8–34.8) for males and females respectively. MS incidence has increased over the last 50 years. Cluster analysis showed an SMR of 0.2 (95% CI 0.05–0.68, p = 0.002) on the island of San Pietro, and 2.0 (95% CI 1.35–2.95, p = 0.001) in Domusnovas. Spatial distribution of MS was confirmed by Bayesian geographical analysis. Conclusions: Our data confirm Sardinia as a high-risk area for MS and support the relevance of genetic factors in MS, as evidenced in St Peter Island. However, we found an unexpectedly high MS prevalence in one village, in particular in males, suggesting an environmental influence on MS occurrence.

We report our experience in long-term treatment of relapsing remitting multiple sclerosis patients with natalizumab (N). In November 2009 we evaluated 141 patients (126 AIFA criterion A, 15 AIFA criterion B). We paid particular attention to the treatment period and the patients follow-up; during the whole therapeutic program, they undergone to clinical and radiological evaluation for every 3 months. The compliance was optimal and we found no significant side effects. 26 patients completed the 24 monthly doses. After 24 months 51% of patients were free from disease activity. We found a reduction in relapses and EDSS, moreover the clinical improvement was also confirmed by radiological examinations. Our results show that the best therapeutic results are achieved by early initiation of treatment.

Conservation biology studies on the endemic species from Sardinia within the "GENMEDOC" Project - The achieved results of the Interreg IIIB "Genmedoc" project (2004-2006) are here reported. Data focused on the conservation biology studies of Sardinian endemic species are showed in this work. During the project 26 populations of 16 species were investigated and the ex situ conservation for these species was guaranteed by storage of 65 seed lots in the seedbank. Furthermore 8 species were analysed by in situ characterization of 17 populations: for each population ecological studies were carried out. Real and possible threats that affect these populations were detected. For 6 species effective germination protocols were identified and also valied by other two project partners. These protocols allow evaluating seed quality for the stored lots and their longevity during next years; moreover the knowledge of the best germination conditions will be able to schedule a possible cultivation or an in situ re-introduction for these species. These results were obtained by sistematic conservation biology studies of threatened endemic species of Sardinia by a tested and internationally acknowledged methodology.

RIASSUNTO. La flora vascolare della Penisola del Sinis (Sardegna Occidentale). Viene presentatolo studio della flora vascolare della Penisola del Sinis; in totale sono state rinvenute 760 unitàtassonomiche e in particolare 615 specie, 134 sottospecie, 10 varietà e 1 ibrido, riferibili a 365 generie 87 famiglie. Le Eudicots sono risultate il gruppo sistematico dominante. Le famiglie più rappresentatesono: Poaceae (99 unità tassonomiche), Fabaceae e Asteraceae (85), Caryophyllaceae (33), Apiaceae(27) e Orchidaceae (24). I generi con maggior numero di taxa sono: Trifolium (19), Silene (14),Limonium e Medicago (13), Ophrys (12), Euphorbia e Vicia (10), Plantago (9), Allium (8) e infineLotus, Ranunculus e Vulpia (7). Il contingente delle endemiche (54 unità tassonomiche) è risultatopari al 8,97% della componente mediterranea e mostra una dominanza degli elementi sardo-corsi(33,33%) e secondariamente sardi (24,10%), i quali unitamente raggiungono il 57,43% del totale. Laflora endemica è costituita da 31 specie, 17 sottospecie e 6 varietà, inquadrati in 38 generi e 22famiglie. Le famiglie più rappresentate sono risultate le Plumbaginaceae (10), Asteraceae e Lamiaceae(5), Fabaceae (4), Alliaceae, Euphorbiaceae e Ranunculaceae (3); il genere più ricco è risultatoLimonium (10), seguito da Allium, Delphinium, Euphorbia, Scrophularia, Silene e Teucrium (2). E’statoelaborato un elenco dei taxa inseriti nelle liste rosse regionali d’Italia, al quale sono state aggiuntetutte le endemiche esclusive e le specie di importanza conservazionistica a livello regionale, per lequali vengono proposte le nuove categorie di protezione secondo i criteri della IUCN. Da tale analisiè emerso che sono presenti 12 unità tassonomiche gravemente minacciate, gruppo che include granparte delle endemiche esclusive del territorio. Sulla base dei dati morfologici, geologici e bioclimaticirelativi ai territori studiati, unitamente alle analisi di tipo floristico ed in particolare della componenteendemica e d’interesse fitogeografico, viene proposto un inquadramento biogeografico a livello disottosettore.Parole chiave. Flora, diversità vegetale, endemiche, conservazione, biogeografia, SardegnaABSTRACT. The vascular flora of Sinis Peninsula (W Sardinia).The vascular flora of Sinis Peninsula(W Sardinia) has been studied; 760 taxa, 615 of which were species, 134 subspecies, 10 varieties and1 hybrid were found. They were included in 365 genera and 87 families. The Eudicots were dominantover the other systematic groups. The most represented families were: Poaceae (99 taxonomic units),Fabaceae and Asteraceae (85), Caryophyllaceae (33), Apiaceae (27) and Orchidaceae (24). The mostrepresented genera were: Trifolium (19), Silene (14), Limonium and Medicago (13), Ophrys (12),Euphorbia and Vicia (10), Plantago (9), Allium (8) and, finally, Lotus, Ranunculus and Vulpia (7). The contingent of endemics (54 taxonomic units) was 8,97% of the Mediterranean component showingthe dominance of Sardinian-Corsican (33,33%) and in the second place Sardinian elements (24,10%),that together to reach 57,43% of the total. This flora consisted of 31 species, 17 subspecies and 6varieties; 38 genera and 22 families were recognized. The most represented families were:Plumbaginaceae (10), Asteraceae and Lamiaceae (5), Fabaceae (4), Alliaceae, Euphorbiaceae andRanunculaceae (3). The most represented genera were: Limonium (10) and Allium, Delphinium,Euphorbia, Scrophularia, Silene, Teucrium (2). Based on the taxa present in the regional Italian RedList, the species exclusive of Sardinia and important for the conservation has been included. Forthese species we proposed the news categories of preservation following the IUCN criteria. Ouranalysis, confirmed the presence of 12 taxa critically endangered as well as this group included themajority of exclusive endemism of the territory. According to the geomorphological, geological andbioclimatic data of the territories studied within the floristic analysis and in particular the endemicand phytogeographical component, we proposed the creation of new biogeographic subsector namedSinisico.Key words. Flora, plants diversity, endemics, conservation, biogeography, Sardinia

Contents, activities in progress and results achieved of a project on the conservation of the plant diversity of the Protected Sea Area of Capo Carbonara, funded in 2005 by the Ministry of Environment and Territory Protection are illustrated.

We performed a case-control study in 2,555 multiple sclerosis (MS) Sardinian patients and 1,365 healthy ethnically matched controls, analyzing the interactions between HLA-DRB1-DQB1 haplotypes and defining a rank of genotypes conferring a variable degree of risk to the disease. Four haplotypes were found to confer susceptibility (*13:03-*03:01 OR = 3.3, Pc 5.1 × 10(-5), *04:05-*03:01 OR = 2.1, Pc 9.7 × 10(-8), *15:01-*06:02 OR = 2.0, Pc = 9.1 × 10(-3), *03:01-*02:01 OR = 1.7 Pc = 7.9 × 10(-22)) and protection (*11, OR = 0.8, Pc = 2.7 × 10(-2), *16:01-*05:02 OR = 0.6, Pc = 4.8 × 10(-16), *14:01-4-*05:031 = OR = 0.5, Pc = 9.8 × 10(-4) and *15:02-*06:01 OR = 0.4, Pc = 5.1 × 10(-4)). The relative predispositional effect method confirms all the positively associated haplotypes and showed that also *08 and *04 haplotypes confers susceptibility, while the *11 was excluded as protective haplotype. Genotypic ORs highlighted two typologies of interaction between haplotypes: i) a neutral interaction, in which the global risk is coherent with the sum of the single haplotype risks; ii) a negative interaction, in which the genotypic OR observed is lower than the sum of the OR of the two haplotypes. The phylogenic tree of the MS-associated DRB1 alleles found in Sardinian patients revealed a cluster represented by *14:01, *04:05, *13∶03, *08:01 and *03:01 alleles. Sequence alignment analysis showed that amino acids near pocket P4 and pocket P9 differentiated protective from predisposing alleles under investigation. Furthermore, molecular dynamics simulation performed on alleles revealed that position 70 is crucial in binding of MBP 85-99 peptide. All together, these data suggest that propensity to MS observed in Sardinian population carried by the various HLA-DRB1-DQB1 molecules can be due to functional peculiarity in the antigen presentation mechanisms.

The new species Aquilegia cremnophila (Ranunculaceae) from the Italian island of Sardinia is here described and illustrated. It occurs in shady rocky crevices, near the upper parts of Mt. Corrasi (Supramontes Region), where it is a member of chasmophilous communities. This species is morphologically, phenologically, ecologically and genetically well differentiated from the other Sardinian taxa, showing some relationships mainly with A. nugorensis, an endemic species of Central-Eastern Sardinia. Its conservation status is examined. A key of all taxa present in Sardinia is also provided.

FENU, G., E. MATTANA, A. CONGIU & G. BACCHETTA (2010). The endemic vascular flora of Supramontes (Sardinia), a priority plant conservation area. Candollea 65: 347–358. In English, English and French abstracts. The main aim of this work is to present a checklist of the endemic vascular flora of the Supramontes region (Central Eastern Sardinia) in order to classify this area in the Sardinian biogeographic subprovince and to better assess its conservation priorities. It is one of the most interesting regions of the Island and spreads for 335 km2 from the inland limestone massif to the Orosei gulf. This work was based on bibliographic and herbarium studies, integrated by several field surveys carried out from 2004 to 2009. In this study 138 endemic taxa, belonging to 98 genera and 42 families, have been found, with 92 of which being species, 40 subspecies, 5 varieties and 1 hybrid. The analysis of biologic and chorologic data highlighted the peculiarities of this territory. Due to the relatively high...

Multiple sclerosis (MS) is a chronic demyelinating disease affecting the central nervous system. Pharmacological therapy of MS includes symptomatic drugs, treatment for relapses (corticosteroid and intravenous immunoglobulin) and disease modifying drugs (DMDs) defined as pharmacological agents that have an impact on relapse rate, disability accumulation and radiological outcomes. Two different therapeutic approaches are widely used in MS: escalation and induction therapy. Escalation therapy consists of an early start with first line DMDs (beta interferon, glatiramer acetate, teriflunomide, dimethyl fumarate) and if DMDs are ineffective or partially effective, switching to second line drugs (mitoxantrone, natalizumab, fingolimod). Induction therapy consists of the early use of immunosuppressant drugs followed by long-term maintenance treatment, generally with immunomodulatory agents. While the use of natalizumab and fingolimod as first line drugs is indicated for aggressive forms of MS, the indication for mitoxantrone as an induction treatment arises from randomized studies demonstrating that induction therapy with mitoxantrone followed by DMD maintenance is more effective than monotherapy with beta interferon. However, the safety profile of induction drugs indicates this is not an acceptable therapeutic strategy for all MS patients in all phases of the disease. The upcoming challenge is to identify patients at high risk of disability development from their clinical characteristics, radiological findings or biomarkers. Furthermore, future studies to establish an individual safety profile stratification are needed.

A study on the vascular flora of the Gennargentu Massif (Central-Eastern Sardinia) is presented. According to our results, the flora consists of 948 taxa: 686 species, 249 sub- species, 10 varieties and 3 hybrids, belonging to 97 families and 427 genera. Three taxa are new findings for the flora of Italy and eight for that of Sardinia. Life form analysis revealed, in particular, dominance of 35.65 % hemicryptophytes, 34.6 % therophytes, 12.13 % geophytes and 11.6 % (nano)-phanero- phytes. As concerns chorology, the Mediterranean element is largely prevailing (68.14%), mainly represented by circum- Medit. (29.1 %) and Euro-Medit. (23.07 %). Endemics are 14.87% of the whole flora (141 taxa), with a large prevalence of Sardo-Corsican (39.01 %) and Sardinian taxa (35.46 %), i.e. 74.47% of the total. Due to the high number of taxa (9) of Gennargentu exclusive endemics and the geologic and geo- morphologic peculiarities, it is here proposed a biogeographic classification for these territories serving to the identification of an autonomous sector. L’étude de la flore vasculaire du massif du Gennargentu (Sardaigne centre-est) est présentée. Les investigations floris- tiques ont établi la présence de 948 taxa, dont 686 espèces, 249 sous-espèces, 10 variétés et 3 hybrides, appartenant a 97 familles et 427 genres. Trois nouveaux taxa sont signalés pour la flore d’Italie et huit pour la flore Sarde. L’analyse du spectre biologique établit, en particulier, la dominance d’hémicryptophytes (35,65 %), de thérophytes (34,6 %), de géophytes (12,13 %) et de (nano-)phanérophytes (11,6 %). L’analyse du spectre chorologique met en évidence la prédo- minance de composantes méditerranéennes (68,14 %), princi- palement représentées par des taxa circum-méditerranéens (29,1 %) et euro-méditerranéens (23,07 %). Les entités endé- miques représentent 14,87% (141 taxa) de la flore, avec une majorité d’éléments corsico-sardes (39,01%) et sardes (35,46%) formant ensemble 74,47% des endémiques. En raison du nombre élevé de taxa (9) d’espèces endémiques exclusives du Gennargentu et des particularités géologiques et géomorpho- logiques, une classification biogéographique est proposée pour ces territoires servant à l’identification d’un secteur autonome.

In 2011, MATTM and SBI started a collaboration for the New Red List of Italian Vascular Flora, according to the IUCN Categories and Criteria. IUCN Red Lists represent the most widely applied protocol for evaluating species extinction risk, because they facilitate objective and replicable assessments. National assessments provide a basis for conservation planning, representing an important starting points for further conservation actions. Data on species distribution gathered, from recent field surveys, herbarium specimens, published and unpublished data, were assembled with the collaboration of a large number of SBI members. All georeferenced records were validated by a selected group of botanists and organized in a 2 × 2 km cells grid in GIS environment. A database including distribution data, population trends and the main threats affecting taxa was developed. All the assessments were validated during several collective workshops. During 2016, the New Red List of the Italian Vascular Flora will be completed with the evaluation of more than 2000 taxa including Italian Policy species (152 taxa, listed in the annexes of Directive 92/43/CEE “Habitat” and Bern Convention), all Italian endemics (more than 1200 taxa, most part of taxonomically critical genera as Alchemilla, Hieracium, Pilosella, Ranunculus, Rubus and Taraxacum excluded) and all those species of potential conservation interest listed in 2012 for MATTM (more than 1500 taxa, some endemics included). Here, we present the updated status, in view of the ultimate goal that will be reached by the end of 2016. The publication of a book that will summarize all the work done is foreseen for 2017.