Volume and carbonate production estimates of early Palaeogene calcareous nannofossils

To assess the role played in the carbonate budget by calcifying phytoplanktonic organisms, it is necessary to provide reliable quantitative estimates of the calcite secreted by calcareous nannoplankton, which certainly have had a vital role in the global carbon cycle since the Jurassic by supplying organic carbon and calcium carbonate to the deep ocean. Reconstructed volume/mass estimates of early Palaeogene calcareous nannofossils based on previous methodologies/techniques applied to extant nannoplankton and/or fossil assemblages suggest that carbonate produced by specific taxa significantly varies both in time and in space. Changes in the calcite within a single taxon and all the more so in the calcium carbonate produced by the entire assemblage are influenced by modifications of palaeoenvironmental conditions and are used as palaeoecological and/or palaeo‐oceanographic proxy.     

Social isolation-induced increase in alpha and delta subunit gene expression is associated with a greater efficacy of ethanol on steroidogenesis and GABA receptor function

Previously we have demonstrated that social isolation of rats reduces both the cerebrocortical and plasma concentrations of 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG), and potentiates the positive effects of acute ethanol administration on the concentrations of this neurosteroid. We now show that the ethanol-induced increase in 3alpha,5alpha-TH PROG is more pronounced in the brain than in the plasma of isolated rats. The ability of ethanol to inhibit isoniazid-induced convulsions is greater in isolated rats than in group-housed animals and this effect is prevented by treatment with finasteride. Social isolation modified the effects of ethanol on the amounts of steroidogenic regulatory protein mRNA and protein in the brain. Moreover, ethanol increased the amplitude of GABA(A) receptor-mediated miniature inhibitory postsynaptic currents recorded from CA1 pyramidal neurones with greater potency in hippocampal slices prepared from socially isolated rats than in those from group-housed rats, an effect inhibited by finasteride. The amounts of the alpha(4) and delta subunits of the GABA(A) receptor in the hippocampus were increased in isolated rats as were GABA(A) receptor-mediated tonic inhibitory currents in granule cells of the dentate gyrus. These results suggest that social isolation results in changes in GABA(A) receptor expression in the brain, and in an enhancement of the stimulatory effect of ethanol on brain steroidogenesis, GABA(A) receptor function and associated behaviour.     

Discovery process and pharmacological characterization of a novel dual orexin 1 and orexin 2 receptor antagonist useful for treatment of sleep disorders

The hypothalamic peptides orexin-A and orexin-B are potent agonists of two G-protein coupled receptors, namely the OX(1) and the OX(2) receptor. These receptors are widely distributed, though differentially, in the rat brain. In particular, the OX(1) receptor is highly expressed throughout the hypothalamus, whilst the OX(2) receptor is mainly located in the ventral posterior nucleus. A large body of compelling evidence, both pre-clinical and clinical, suggests that the orexin system is profoundly implicated in sleep disorders. In particular, modulation of the orexin receptors activation by appropriate antagonists was proven to be an efficacious strategy for the treatment of insomnia in man. A novel, drug-like bis-amido piperidine derivative was identified as potent dual OX(1) and OX(2) receptor antagonists, highly effective in a pre-clinical model of sleep.     

Single exposure of human fibroblasts (WI-38) to a sub-cytotoxic dose of UVB induces premature senescence

In this work, we present a new model of stress-induced premature senescence obtained by exposing human fibroblasts (WI-38) at early passages (passages 2-4) to a single sub-cytotoxic dose of UVB (200 mJ/cm(2)). We show that this treatment leads to the appearance of several biomarkers of senescence such as enlarged and flattened cell morphology, the presence of nuclear heterochromatic foci and beta-galactosidase activity. Furthermore, we demonstrate that a mild ROS production and p53 activation are upstream events required for the induction of premature senescence. Our method represents an alternative in vitro model in photoaging research and could be used to test potential anti-photoaging compounds.     

Colonoscopic surveillance of first-degree relatives of colorectal cancer patients in a faecal occult blood screening programme

Background: In some Italian areas, colonoscopic surveillance of first-degree relatives (FDRs) of colorectal cancer (CRC) patients is provided as a part of local population-based faecal occult blood test (FOBT) screening programmes. The objective of the present study was to assess the feasibility and early results of this surveillance model. Methods: Data from district screening centres were used to evaluate the process of identification and selection of eligible FDRs (residence in the Emilia-Romagna Region, age 40–75 years, no recent colonoscopy) of screen-detected CRC patients and the detected prevalence of disease. The probability for an FDR to undergo colonoscopy and to be diagnosed with CRC and advanced adenoma was estimated using the Kaplan–Meier method. The sex- and age-standardised ratio of detected prevalence to that expected based on results from a colonoscopy screening study of the Italian general population was estimated. Results: Between 2005 and 2011, 9319 FDRs of 2437 screen-detected CRC patients (3.8 per patient) were identified and contacted. Their likelihood of being eligible for, and accepting, colonoscopy was 0.11 (95% confidence interval: 0.11–0.12). Among the 926 subjects undergoing colonoscopy, the prevalence of previous negative screening FOBT was 63%. Eleven CRCs (1.2%) and 100 advanced adenomas (10.8%) were detected. The standardised ratio of detected prevalence to that expected was 0.91 (95% confidence interval: 0.19–2.66) for CRC and 1.48 (1.04–2.05) for advanced adenoma. Conclusions: The procedure of selection of FDRs was extremely ineffective. Due to previous negative screening tests, the prevalence of disease was less than expected. A population-based FOBT screening programme is a highly unsuitable setting for the provision of surveillance to FDRs of CRC patients.     

The presence of a p53-like protein during pea seed maturation and germination

ABSTRACT

The mechanisms that allow monitoring of DNA damage and the activation of repair systems in plants are poorly known. In mammalian cells the tumor suppressor protein p53 plays an important role in the checkpoint pathway induced by DNA damage. In this work, we investigated the presence and distribution of the p53-like protein in pea root tip nuclei and its role during early germination in relation to DNA damage. In pea seed, PFGE and TdT assays show that DNA fragmentation occurs during maturation and dry seed storage, and that this DNA fragmentation is repaired at the beginning of germination before the onset of proliferation. In the same seeds, the p53-like protein was found during maturation and germination. Immunoblotting characterization of this protein led to the identification of a single specific protein of about 94 kDa, more abundant at the beginning of the hydration process than in actively cycling cells. Furthermore, the p53-like protein revealed different nuclear distribution patterns, probably in relation to the formation of DNA fragments in dry seeds, and to the reactivation of repair mechanisms during early germination. These data suggest that the presence of a p53-like protein in quiescent or proliferating pea embryo cells is related to DNA damage, and serves for the maintenance of genetic information and the development of normal seedlings.     

Motor Imagery in Asperger Syndrome: Testing Action Simulation by the Hand Laterality Task

Asperger syndrome (AS) is a neurodevelopmental condition within the Autism Spectrum Disorders (ASD) characterized by specific difficulties in social interaction, communication and behavioural control. In recent years, it has been suggested that ASD is related to a dysfunction of action simulation processes, but studies employing imitation or action observation tasks provided mixed results. Here, we addressed action simulation processes in adolescents with AS by means of a motor imagery task, the classical hand laterality task (to decide whether a rotated hand image is left or right); mental rotation of letters was also evaluated. As a specific marker of action simulation in hand rotation, we assessed the so-called biomechanical effect, that is the advantage for judging hand pictures showing physically comfortable versus physically awkward positions. We found the biomechanical effect in typically-developing participants but not in participants with AS. Overall performance on both hand laterality and letter rotation tasks, instead, did not differ in the two groups. These findings demonstrated a specific alteration of motor imagery skills in AS. We suggest that impaired mental simulation and imitation of goal-less movements in ASD could be related to shared cognitive mechanisms.