PALEOMAGNETIC AND PALYNOLOGIC INVESTIGATIONS IN THE UPPER VALDARNO BASIN (CENTRAL ITALY): CALIBRATION OF AN EARLY VILLAFRANCHIAN FAUNA

The silty clays embedding an early Villafranchian mammal fauna of the Triversa faunal unit (f.u.) have been paleomagnetically and palynologically studied in a continuous sequence exposed in the Santa Barbara quarry.The study has allowed to date the earliest occurrence in Italy of a faunal assemblage of this unit and to define the corresponding climatic conditions. The sampled section has provided a magnetic polarity sequence of the late Gauss,where the fossiliferous layer fits the Kaena reversed interval.Its age of ca. 3.1 Ma,during subtropical climate conditions correlatable to the Reuverian of Netherlands, suggests an older age for the beginning of the Villafranchian, possibly associated to a more dramatic scenario able to trigger the faunal turnover. &nbsp

Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway

Oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD), an X-linked genetic disorder caused by mutations in the dystrophin gene and characterized by progressive, lethal muscle degeneration and chronic inflammation. In this study, we explored the expression and signaling pathway of a master player of the anti-oxidant and anti-inflammatory response, namely NRF2, in muscle biopsies of DMD patients. We classified DMD patients in two age groups (Class I, 0-2 years and Class II, 2-9 years), in order to evaluate the antioxidant pathway expression during the disease progression. We observed that altered enzymatic antioxidant responses, increased levels of oxidized glutathione and oxidative damage are differently modulated in the two age classes of patients and well correlate with the severity of pathology. Interestingly, we also observed a modulation of relevant markers of the inflammatory response, such as heme oxygenase 1 and IL-6, suggesting a link between oxidative stress and chronic inflammatory response. Of note, using a transgenic mouse model, we demonstrated that IL-6 overexpression parallels the antioxidant expression profile and the severity of dystrophic muscle observed in DMD patients. This study advances our understanding of the pathogenic mechanisms underlying DMD and defines the critical role of oxidative stress on muscle wasting with clear implications for disease pathogenesis and therapy in human

Oxidative stress in Duchenne muscular dystrophy: focus on the NRF2 redox pathway

Oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD), an X-linked genetic disorder caused by mutations in the dystrophin gene and characterized by progressive, lethal muscle degeneration and chronic inflammation. In this study, we explored the expression and signaling pathway of a master player of the anti-oxidant and anti-inflammatory response, namely NRF2, in muscle biopsies of DMD patients. We classified DMD patients in two age groups (Class I, 0-2 years and Class II, 2-9 years), in order to evaluate the antioxidant pathway expression during the disease progression. We observed that altered enzymatic antioxidant responses, increased levels of oxidized glutathione and oxidative damage are differently modulated in the two age classes of patients and well correlate with the severity of pathology. Interestingly, we also observed a modulation of relevant markers of the inflammatory response, such as heme oxygenase 1 and IL-6, suggesting a link between oxidative stress and chronic inflammatory response. Of note, using a transgenic mouse model, we demonstrated that IL-6 overexpression parallels the antioxidant expression profile and the severity of dystrophic muscle observed in DMD patients. This study advances our understanding of the pathogenic mechanisms underlying DMD and defines the critical role of oxidative stress on muscle wasting with clear implications for disease pathogenesis and therapy in human

THE PIONEERING CONTRIBUTIONS AND LEGACY OF WALDO H. ZAGWIJN (1928-2018)

Professor Dr. Waldo H. Zagwijn passed away on 26 June, 2018, in his ninetieth year. His thesis research (Zagwijn, 1960) stimulated palynological investigations into the Pliocene and early Quaternary, and caused a fundamental shift in our under-standing of the transition from the warm and relatively stable climate of the late Neogene to the extreme glacial-interglacial oscilla-tions of the early Quaternary. Distinct in several aspects from the usual methodologies of that time, Zagwijn’s approach can be summarized as: focusing on establishing the botanical identification of pollen grains, following the guiding approach of his supervisor F. Flor-schütz, using botanical nomenclature to highlight these identifications and clarifying relationships between botany and the ear-lier artificial pollen nomenclature; comprehensive and continuous attention to plant macroremains (fruits, seeds, etc.; Zagwijn, 1990) as a mean of integrating classical palaeobotany with modern palynology; palaeoenvironmental interpretations informed by a deep understanding of modern plant ecology and associations; leading investigations in the field, and paying special attention to stratigraphic correlations between (onshore and offshore) boreholes and exposed sections in quarries, using a range of available proxies including heavy mineral analysis. Waldo H. Zagwijn was a visionary in realizing how modern palynology can be used for vegetational and climatic reconstructions in the Neogene, and indeed as far back as Paleogene times

miRNAs as serum biomarkers for Duchenne muscular dystrophy

Dystrophin absence in Duchenne muscular dystrophy (DMD) causes severe muscle degeneration. We describe that, as consequence of fibre damage, specific muscle-miRNAs are released in to the bloodstream of DMD patients and their levels correlate with the severity of the disease. The same miRNAs are abundant also in the blood of mdx mice and recover to wild-type levels in animals ‘cured’ through exon skipping. Even though creatine kinase (CK) blood levels have been utilized as diagnostic markers of several neuromuscular diseases, including DMD, we demonstrate that they correlate less well with the disease severity. Although the analysis of a larger number of patients should allow to obtain more refined correlations with the different stages of disease progression, we propose that miR-1, miR-133, and miR-206 are new and valuable biomarkers for the diagnosis of DMD and possibly also for monitoring the outcomes of therapeutic interventions in humans. Despite many different DMD therapeutic approaches are now entering clinical trials, a unifying method for assessing the benefit of different treatments is still lacking

Myotonia permanens with Nav1.4-G1306E displays varied phenotypes during course of life

Myotonia permanens due to Nav1.4-G1306E is a rare sodium channelopathy with potentially life-threatening respiratory complications. Our goal was to study phenotypic variability throughout life