SYNTHESIS OF CALCAREOUS NANNOFOSSIL EVENTS IN TETHYAN LOWER AND MIDDLE JURASSIC SUCCESSIONS

This paper is a synthesis of calcareous nannofossil biostratigraphy for the Lower and Middle Jurassic of the Mediterranean Province based on several sections from Northern and Central Italy. Nannofossil events were calibrated with ammonite biostratigraphy and, when necessary, ammonite-controlled sections in South East France were incorporated. Data derive from previously published biostratigraphies and unpublished data of the authors.The large data-set allowed estimates of reliability and reproducibility of single events. As a result, in the Hettangian-Bathonian interval we propose 47 main events based on diagenesis-resistant and common taxa, 17 events based on rare but ubiquitous taxa and 12 potential events requiring further investigations due to taxonomic problems and sporadic occurrence. A biostratigraphic scheme, consisting of 11 zones and 15 subzones, is proposed for the Tethyan Lower and Middle Jurassic. The proposed biostratigraphy is compared to recent schemes compiled for Portugal, Morocco, Switzerland and the Boreal Realm. Only 27 events are reproducible in various regions, but diachroneity of most events seems to derive from different ammonite biostratigraphies applied in different areas. A very high stratigraphic resolution is achieved in Italy/France for the Pliensbachian to Lower Bajocian interval. The Sinemurian and Bathonian are characterized by the lowest resolution, and very few sections with ammonite control and/or favourable lithologies are available for improvement of nannofossil biostratigraphy. This study confirms the potential of calcareous nannofossil biostratigraphy for dating Lower and Middle Jurassic successions as well as for intra- and inter-regional correlations.&nbsp

Altered modulation of lamin A/C-HDAC2 interaction and p21 expression during oxidative stress response in HGPS

Defects in stress response are main determinants of cellular senescence and organism aging. In fibroblasts from patients affected by Hutchinson-Gilford progeria, a severe LMNA-linked syndrome associated with bone resorption, cardiovascular disorders, and premature aging, we found altered modulation of CDKN1A, encoding p21, upon oxidative stress induction, and accumulation of senescence markers during stress recovery. In this context, we unraveled a dynamic interaction of lamin A/C with HDAC2, an histone deacetylase that regulates CDKN1A expression. In control skin fibroblasts, lamin A/C is part of a protein complex including HDAC2 and its histone substrates; protein interaction is reduced at the onset of DNA damage response and recovered after completion of DNA repair. This interplay parallels modulation of p21 expression and global histone acetylation, and it is disrupted by LMNAmutations leading to progeroid phenotypes. In fact, HGPS cells show impaired lamin A/C-HDAC2 interplay and accumulation of p21 upon stress recovery. Collectively, these results link altered physical interaction between lamin A/C and HDAC2 to cellular and organism aging. The lamin A/C-HDAC2 complex may be a novel therapeutic target to slow down progression of progeria symptoms

Statins and histone deacetylase inhibitors affect lamin A/C - histone deacetylase 2 interaction in human cells

We recently identified lamin A/C as a docking molecule for human histone deacetylase 2 (HDAC2) and showed involvement of HDAC2-lamin NC complexes in the DNA damage response. We further showed that lamin NC-HDAC2 interaction is altered in Hutchinson-Gilford Progeria syndrome and other progeroid laminopathies. Here, we show that both inhibitors of lamin A maturation and small molecules inhibiting HDAC activity affect lamin NC interaction with HDAC2. While statins, which inhibit prelamin A processing, reduce protein interaction, HDAC inhibitors strengthen protein binding. Moreover, treatment with HDAC inhibitors restored the enfeebled lamin NC-HDAC2 interaction observed in HGPS cells. Based on these results, we propose that prelamin A levels as well as HDAC2 activation status might influence the extent of HDAC2 recruitment to the lamin A/C-containing platform and contribute to modulate HDAC2 activity. Our study links prelamin A processing to HDAC2 regulation and provides new insights into the effect of statins and histone deacetylase inhibitors on lamin NC functionality in normal and progeroid cells

Effects on Collagen VI mRNA Stability and Microfibrillar Assembly of Three COL6A2 Mutations in Two Families with Ullrich Congenital Muscular Dystrophy

We recently reported a severe deficiency in collagen type VI, resulting from recessive mutations of the COL6A2 gene, in patients with Ullrich congenital muscular dystrophy. Their parents, who are all carriers of one mutant allele, are unaffected, although heterozygous mutations in collagen VI caused Bethlem myopathy. Here we investigated the consequences of three COL6A2 mutations in fibroblasts from patients and their parents in two Ullrich families. All three mutations lead to nonsense-mediated mRNA decay. However, very low levels of undegraded mutant mRNA remained in patient B with compound heterozygous mutations at the distal part of the triple-helical domain, resulting in deposition of abnormal microfibrils that cannot form extensive networks. This observation suggests that the C-terminal globular domain is not essential for triple-helix formation but is critical for microfibrillar assembly. In all parents, the COL6A2 mRNA levels are reduced to 57-73% of the control, but long term collagen VI matrix depositions are comparable with that of the control. The almost complete absence of abnormal protein and near-normal accumulation of microfibrils in the parents may account for their lack of myopathic symptoms

Statins and Histone Deacetylase Inhibitors Affect Lamin A/C – Histone Deacetylase 2 Interaction in Human Cells

We recently identified lamin A/C as a docking molecule for human histone deacetylase 2 (HDAC2) and showed involvement of HDAC2-lamin A/C complexes in the DNA damage response. We further showed that lamin A/C-HDAC2 interaction is altered in Hutchinson-Gilford Progeria syndrome and other progeroid laminopathies. Here, we show that both inhibitors of lamin A maturation and small molecules inhibiting HDAC activity affect lamin A/C interaction with HDAC2. While statins, which inhibit prelamin A processing, reduce protein interaction, HDAC inhibitors strengthen protein binding. Moreover, treatment with HDAC inhibitors restored the enfeebled lamin A/C-HDAC2 interaction observed in HGPS cells. Based on these results, we propose that prelamin A levels as well as HDAC2 activation status might influence the extent of HDAC2 recruitment to the lamin A/C-containing platform and contribute to modulate HDAC2 activity. Our study links prelamin A processing to HDAC2 regulation and provides new insights into the effect of statins and histone deacetylase inhibitors on lamin A/C functionality in normal and progeroid cells

dysferlin in a hyperckaemic patient with caveolin 3 mutation and in c2c12 cells after p38 map kinase inhibition

Dysferlin is a plasma membrane protein of skeletal muscle whose deficiency causes Miyoshi myopathy, limb girdle muscular dystrophy 2B and distal anterior compartment myopathy. Recent studies have reported that dysferlin is implicated in membrane repair mechanism and coimmunoprecipitates with caveolin 3 in human skeletal muscle. Caveolin 3 is a principal structural protein of caveolae membrane domains in striated muscle cells and cardiac myocytes. Mutations of caveolin 3 gene (CAV3) cause different diseases and where caveolin 3 expression is defective, dysferlin localization is abnormal. We describe the alteration of dysferlin expression and localization in skeletal muscle from a patient with raised serum creatine kinase (hyperCKaemia), whose reduction of caveolin 3 is caused by a CAV3 P28L mutation. Moreover, we performed a study on dysferlin interaction with caveolin 3 in C2C12 cells. We show the association of dysferlin to cellular membrane of C2C12 myotubes and the low affinity link between dysferlin and caveolin 3 by immunoprecipitation techniques. We also reproduced caveolinopathy conditions in C2C12 cells by a selective p38 MAP kinase inhibition with SB203580, which blocks the expression of caveolin 3. In this model, myoblasts do not fuse into myotubes and we found that dysferlin expression is reduced. These results underline the importance of dysferlin-caveolin 3 relationship for skeletal muscle integrity and propose a cellular model to clarify the dysferlin alteration mechanisms in caveolinopathies

Failure of lamin A/C to functionally assemble in R482L mutated familial partial lipodystrophy fibroblasts: altered intermolecular interaction with emerin and implications for gene transcription

Familial partial lipodystrophy is an autosomal dominant disease caused by mutations of the LMNA gene encoding alternatively spliced lamins A and C. Abnormal distribution of body fat and insulin resistance characterize the clinical phenotype. In this study, we analyzed primary fibroblast cultures from a patient carrying an R482L lamin A/C mutation by a morphological and biochemical approach. Abnormalities were observed consisting of nuclear lamin A/C aggregates mostly localized close to the nuclear lamina. These aggregates were not bound to either DNA-containing structures or RNA splicing intranuclear compartments. In addition, emerin did not colocalize with nuclear lamin A/C aggregates. Interestingly, emerin failed to interact with lamin A in R482L mutated fibroblasts in vivo, while the interaction with lamin C was preserved in vitro, as determined by coimmunoprecipitation experiments. The presence of lamin A/C nuclear aggregates was restricted to actively transcribing cells, and it was increased in insulin-treated fibroblasts. In fibroblasts carrying lamin A/C nuclear aggregates, a reduced incorporation of bromouridine was observed, demonstrating that mutated lamin A/C in FPLD cells interferes with RNA transcription

Current Knowledge on Selenium Biofortification to Improve the Nutraceutical Profile of Food: A Comprehensive Review

Selenium (Se) is an important micronutrient for living organisms, since it is involved in several physiological and metabolic processes. Se intake in humans is often low and very seldom excessive, and its bioavailability depends also on its chemical form, with organic Se as the most available after ingestion. The main dietary source of Se for humans is represented by plants, since many species are able to metabolize and accumulate organic Se in edible parts to be consumed directly (leaves, flowers, fruits, seeds, and sprouts) or after processing (oil, wine, etc.). Countless studies have recently investigated the Se biofortification of plants to produce Se-enriched foods and elicit the production of secondary metabolites, which may benefit human health when incorporated into the diet. Moreover, feeding animals Se-rich diets may provide Se-enriched meat. This work reviews the most recent literature on the nutraceutical profile of Se-enriched foods from plant and animal sources.Fil: D'Amato, Roberto. Università di Perugia; ItaliaFil: Regni, Luca. Università di Perugia; ItaliaFil: Falcinelli, Beatrice. Università di Perugia; ItaliaFil: Mattioli, Simona. Università di Perugia; ItaliaFil: Benincasa, Paolo. Università di Perugia; ItaliaFil: Dal Bosco, Alessandro. Università di Perugia; ItaliaFil: Pacheco, Pablo Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Proietti, Primo. Università di Perugia; ItaliaFil: Troni, Elisabetta. Università di Perugia; ItaliaFil: Santi, Claudio. Università di Perugia; ItaliaFil: Businelli, Daniela. Università di Perugia; Itali

ELENA instrument science and testing: validation with particle beam

Understanding of particle emission processes from the Mercury surface is one of the major objectives of ELENAinstrument in the SERENA experiment on board of the BepiColombo mission. In particular the Ion-Sputteringprocess resulting from charged and energetic particles impacting on the surface can be investigated detectingthe low energetic neutral particles escaping from the planet. The possibility to identify the Ion-Sputtering signaltogether with back-scattered particles and neutrals generated by charge exchange is strictly linked with the newtechnology capability to measure low energetic neutral atoms. This goal can be addressed thanks to a new&oldapproach for the neutral atoms measurement: a well known Time of Flight system enhanced with a new kind ofStart section able to define the start time of the entrance in the ToF path without interacting with the particles anddirectly follow to the Stop detector. The Start section is a shutter composed by two membranes with nanometricslits realized in a large area (1cm2) and oscillating at several frequencies to open and close the entrance of ToFsection. This system is never used before in space mission.The IFSI-INAF Ion beam facility in Rome is devoted to the ELENA testing. The crucial point of the shutteringsystem interaction with particle beam is investigated. The first results demonstrate the good functionality of thiskind of system: capability of the shutter to Open and Close the entrance respect to an ion beam is tested with aMCP stop detector. In this poster we present the IFSI activity in the frame of ELENA science requirement togetherwith the experimental activity devoted to instrument verification

Cell damage induced by asbestos similar particles

The presence, in nature, of asbestos similar particles, highly toxic and potentially cancerogenic for human healthy is well known (1). Inhalation of the fibrous form of erionite, has been shown to cause effects compared to those observed with mineral fibers classified as ‘‘asbestos,’’ including malignant mesothelioma, a disease typically associated with occupational and environmental exposures to asbestos (2). In this work various zeolite materials have been considered because of their suspected carcinogenic activity and, the possible interactions occurring between asbestiform fibers and U937 cell, a human hemopoietic cell line, have been evaluated. Chemical and morpho-functional analyses have been carried out, both to characterize fiber structure and cell response. Cells showed the ability to internalize the minerals, as observed after TEM analyses. With zeolite exposure time increasing, a diffuse cell damage with features of apoptotic and necrotic death can be evidenced (3). These findings suggest that the fibrous form of scolecite or offretite too can be considered potentially toxic for cell culture in vitro