Histone deacetylases: molecular mechanisms and therapeutic implications for muscular dystrophies

Histone deacetylases (HDACs) are enzymes that regulate the deacetylation of numerous histone and non-histone proteins, thereby affecting a wide range of cellular processes. Deregulation of HDAC expression or activity is often associated with several pathologies, suggesting potential for targeting these enzymes for therapeutic purposes. For example, HDAC expression and activity are higher in dystrophic skeletal muscles. General pharmacological blockade of HDACs, by means of pan-HDAC inhibitors (HDACi), ameliorates both muscle histological abnormalities and function in preclinical studies. A phase II clinical trial of the pan-HDACi givinostat revealed partial histological improvement and functional recovery of Duchenne Muscular Dystrophy (DMD) muscles; results of an ongoing phase III clinical trial that is assessing the long-term safety and efficacy of givinostat in DMD patients are pending. Here we review the current knowledge about the HDAC functions in distinct cell types in skeletal muscle, identified by genetic and -omic approaches. We describe the signaling events that are affected by HDACs and contribute to muscular dystrophy pathogenesis by altering muscle regeneration and/or repair processes. Reviewing recent insights into HDAC cellular functions in dystrophic muscles provides new perspectives for the development of more effective therapeutic approaches based on drugs that target these critical enzymes

UPDATING THE TAXONOMY AND DISTRIBUTION OF THE EUROPEAN OSMODERMA, AND STRATEGIES FOR THEIR CONSERVATION (COLEOPTERA, SCARABAEIDAE, CETONIINAE)

Results of a molecular analysis on the European hermit beetles (the Osmoderma eremita species-complex), recently published in a companion paper, are shortly dis- cussed and commented. These results indicate a clear-cut distinction between two clades. The first one includes the W-European O. eremita Scopoli, 1763, and the two Italian endemic taxa O. italicum Sparacio, 2000 and O. cristinae Sparacio, 1994, from southern peninsular Italy and Sicily, respectively. The second one includes the widespread E-European O. barnabita Motschulsky, 1845 (nom. resurr.), and the southern Balcanic O. lassallei Baraud & Tauzin, 1991 from Greece and European Turkey. Within the two clades, molecular data well support a specific rank for O. lassallei and O. barn­abita on one side, and of O. eremita and O. cristinae on the other side, while the taxonomic position of O. italicum, more closely related with O. eremita, is still uncertain, waiting for analysis of additional specimens of this very rare taxon. Current geographical distribution, interspecific genetic diversification, and relatively low levels of intraspecific genetic divergence in O. eremita sensu stricto, are hypothesized to be the result of multiple speciation events (mainly occurred in refugial forest areas of the Italian and Balkan peninsulas and Sicily before and during the Pleistocene glacial peaks), followed by fast post-glacial northward and westward expansion of some species. The need of further genetic data on the rare and threatened hermit beetle species and the importance of more detailed information on their distribution ranges are emphasized and discussed, in order to plan conservation strategies in the near future. An updated worldwide checklist of the species of the genus Osmoderma is finally presented

UPDATING THE TAXONOMY AND DISTRIBUTION OF THE EUROPEAN OSMODERMA, AND STRATEGIES FOR THEIR CONSERVATION (Coleoptera, Scarabaeidae, Cetoniinae)

Results of a molecular analysis on the European hermit beetles (the Osmoderma eremita species-complex), recently published in a companion paper, are shortly dis- cussed and commented. These results indicate a clear-cut distinction between two clades. The first one includes the W-European O. eremita Scopoli, 1763, and the two Italian endemic taxa O. italicum Sparacio, 2000 and O. cristinae Sparacio, 1994, from southern peninsular Italy and Sicily, respectively. The second one includes the widespread E-European O. barnabita Motschulsky, 1845 (nom. resurr.), and the southern Balcanic O. lassallei Baraud & Tauzin, 1991 from Greece and European Turkey. Within the two clades, molecular data well support a specific rank for O. lassallei and O. barn­abita on one side, and of O. eremita and O. cristinae on the other side, while the taxonomic position of O. italicum, more closely related with O. eremita, is still uncertain, waiting for analysis of additional specimens of this very rare taxon. Current geographical distribution, interspecific genetic diversification, and relatively low levels of intraspecific genetic divergence in O. eremita sensu stricto, are hypothesized to be the result of multiple speciation events (mainly occurred in refugial forest areas of the Italian and Balkan peninsulas and Sicily before and during the Pleistocene glacial peaks), followed by fast post-glacial northward and westward expansion of some species. The need of further genetic data on the rare and threatened hermit beetle species and the importance of more detailed information on their distribution ranges are emphasized and discussed, in order to plan conservation strategies in the near future. An updated worldwide checklist of the species of the genus Osmoderma is finally presented

How microanalysis can be discriminant on black Pompeian wares

In the present work the advantages of punctual approaches are discussed in the discrimination of black wares from the Sanctuary of Venus Fisica (Pompeii, Italy), dated between the 2nd and 1st century BC. Black-gloss ware and "bucchero" samples are analyzed by a multi-analytical approach including optical microscopy (OM), X-ray powder diffraction (XRPD), scanning electron microscopy with Energy Dispersive Spectroscopy (SEM-EDS) and electron microprobe analysis (EMPA) to investigate the mineralogical and petrographic features of these artefacts. Grain size, firing conditions and potter’s expertise influenced the final appearance of the superficial decorative black layer. In addition, punctual chemical analysis was fundamental to verify the archaeological indication of specific production sites

European Atlas of Natural Radiation

Natural ionizing radiation is considered as the largest contributor to the collective effective dose received by the world population. The human population is continuously exposed to ionizing radiation from several natural sources that can be classified into two broad categories: high-energy cosmic rays incident on the Earth’s atmosphere and releasing secondary radiation (cosmic contribution); and radioactive nuclides generated during the formation of the Earth and still present in the Earth’s crust (terrestrial contribution). Terrestrial radioactivity is mostly produced by the uranium and thorium radioactive families together with potassium. In most circumstances, radon, a noble gas produced in the radioactive decay of uranium, is the most important contributor to the total dose. This Atlas aims to present the current state of knowledge of natural radioactivity, by giving general background information, and describing its various sources. This reference material is complemented by a collection of maps of Europe displaying the levels of natural radioactivity caused by different sources. It is a compilation of contributions and reviews received from more than 80 experts in their field: they come from universities, research centres, national and European authorities and international organizations. This Atlas provides reference material and makes harmonized datasets available to the scientific community and national competent authorities. In parallel, this Atlas may serve as a tool for the public to: • familiarize itself with natural radioactivity; • be informed about the levels of natural radioactivity caused by different sources; • have a more balanced view of the annual dose received by the world population, to which natural radioactivity is the largest contributor; • and make direct comparisons between doses from natural sources of ionizing radiation and those from man-made (artificial) ones, hence to better understand the latter.JRC.G.10-Knowledge for Nuclear Security and Safet

European Atlas of Natural Radiation

Natural ionizing radiation is considered as the largest contributor to the collective effective dose received by the world population. The human population is continuously exposed to ionizing radiation from several natural sources that can be classified into two broad categories: high-energy cosmic rays incident on the Earth’s atmosphere and releasing secondary radiation (cosmic contribution); and radioactive nuclides generated during the formation of the Earth and still present in the Earth’s crust (terrestrial contribution). Terrestrial radioactivity is mostly produced by the uranium and thorium radioactive families together with potassium. In most circumstances, radon, a noble gas produced in the radioactive decay of uranium, is the most important contributor to the total dose.This Atlas aims to present the current state of knowledge of natural radioactivity, by giving general background information, and describing its various sources. This reference material is complemented by a collection of maps of Europe displaying the levels of natural radioactivity caused by different sources. It is a compilation of contributions and reviews received from more than 80 experts in their field: they come from universities, research centres, national and European authorities and international organizations.This Atlas provides reference material and makes harmonized datasets available to the scientific community and national competent authorities. In parallel, this Atlas may serve as a tool for the public to: • familiarize itself with natural radioactivity;• be informed about the levels of natural radioactivity caused by different sources;• have a more balanced view of the annual dose received by the world population, to which natural radioactivity is the largest contributor;• and make direct comparisons between doses from natural sources of ionizing radiation and those from man-made (artificial) ones, hence to better understand the latter.Additional information at: https://remon.jrc.ec.europa.eu/About/Atlas-of-Natural-Radiatio

Functional Nutrients to Ameliorate Neurogenic Muscle Atrophy

Neurogenic muscle atrophy is a debilitating condition that occurs from nerve trauma in association with diseases or during aging, leading to reduced interaction between motoneurons and skeletal fibers. Current therapeutic approaches aiming at preserving muscle mass in a scenario of decreased nervous input include physical activity and employment of drugs that slow down the progression of the condition yet provide no concrete resolution. Nutritional support appears as a precious tool, adding to the success of personalized medicine, and could thus play a relevant part in mitigating neurogenic muscle atrophy. We herein summarize the molecular pathways triggered by denervation of the skeletal muscle that could be affected by functional nutrients. In this narrative review, we examine and discuss studies pertaining to the use of functional ingredients to counteract neurogenic muscle atrophy, focusing on their preventive or curative means of action within the skeletal muscle. We reviewed experimental models of denervation in rodents and in amyotrophic lateral sclerosis, as well as that caused by aging, considering the knowledge generated with use of animal experimental models and, also, from human studies

Terrestrial gamma dose rate mapping (Euganean Hills, Italy): comparison between field measurements and HPGe gamma spectrometric data

Terrestrial gamma radiation is mostly due to radionuclides in soil and rocks, primarily the 238U, 235U and 232Th radioactive families and 40K. This radiation contributes 15% to public exposure from all ionizing radiation sources, considering global population. Moreover, it can be used to estimate radon flux and included as one of the quantities relevant to the geogenic radon hazard model. Therefore, effort has been put into developing maps of terrestrial gamma dose rate at the regional, national or European scale, using different input data and methods. In the present work, two distinct approaches to map terrestrial gamma dose rate have been tested in the Euganean Hills district of NE Italy. The first one is based on 41 in situ measurements of ambient dose equivalent rates using a rate meter equipped with a NaI scintillator probe. The second one estimates terrestrial gamma dose rate from the U, Th and K activity concentrations in rock samples collected at the same locations of the dose rates measurements. The results obtained indicate good agreement between the two approaches, and as such suggest that the UNSCEAR 2008 prescription to derive ambient dose equivalent rate from laboratory gamma measurements produces reliable data, provided that cosmic and fall-out contributions are included. Moreover, the study proved that mapping the ambient dose equivalent rate (or terrestrial gamma dose rate) using only one database – i.e. either measured data or estimates derived from radionuclide activity concentration – yields valid results.JRC.G.10-Knowledge for Nuclear Security and Safet

Radionuclide concentration and radon exhalation in new mix design of bricks produced reusing NORM by-products: the influence of mineralogy and texture

Many industrial by-products contain Naturally Occurring Radioactive Materials (NORM) that normally represent a cost in terms of monitoring, risk management and storage. When included in new mix design of bricks, these materials may become a valuable sustainable resource. Before marketing, companies involved in development and commercialisation of these new building materials ensure safety related to radiation, usually by assessing radon-related risk. According to the Council Directive 2013/59/Euratom, both raw materials and final products used in building constructions need to be tested for activity concentration. The present work explores the radionuclide concentration and the radon exhalation of bricks obtained recycling different types of potentially radioactive wastes: i) trachyte as by-product resulting from quarry operations, and ii) two different types of industrial sludge derived from ceramic tiles industry. Raw materials were studied in order to envisage any potential radioactive risk derived from their use as secondary raw materials, while fired bricks were investigated in order to assess the influence of mineralogy and texture on their radioactive properties and on their effective radon-risk.JRC.G.10-Knowledge for Nuclear Security and Safet

Radionuclide concentration and radon exhalation in new mix design of bricks produced reusing NORM by-products: The influence of mineralogy and texture

Many industrial by-products contain Naturally Occurring Radioactive Materials (NORM) that normallyrepresent a cost in terms of monitoring, risk management and storage. When included in new mix designs of bricks, these materials may become a valuable sustainable resource. Before marketing, companies involved in development and commercialization of these new building materials ensure safety related to radiation, usually by assessing radon-related risk. According to the Council Directive 2013/59/Euratom, both raw materials and final products used in building constructions need to be tested for activity concentration. The present work explores the radionuclide concentration and the radon exhalation of bricks obtained recycling different types of potentially radioactive wastes: i) trachyte as byproduct resulting from quarrying operations, and ii) two different types of industrial sludge derived from ceramic tiles industry. Raw materials were studied to foresee any potential radioactive risk derived from their use as secondary raw materials, while bricks were investigated to assess the influence of mineralogy and texture on their radioactive properties and their effective radon-risk. The results obtained here show that, although radon emanation in bricks is primarily determined by radionuclide concentration in the raw materials, textural features significantly affect radon mobility and exhalation