Preliminary Study of the Mural Paintings of Sotterra Church in Paola (Cosenza,Italy)

A multi-analytical approach was employed to study wall paintings located in the Sotterra church at Paola, in the province of Cosenza, Italy. The site is an underground church (hence the name of Sotterra, which means “under the earth”) rediscovered in the second half of the 19th century, during the building works of the Madonna del Carmine church on the same area. This underground church preserves valuable mural paintings having different styles. The construction’s dating and overlapped modifications made until the site was abandoned is also debated. A wall painting, depicting “The Virgin” as part of the “Annunciation and the Archangel Gabriel” present on the opposite side of the apse, was selected and investigated using both in situ and laboratory-based analysis. Preliminarily, the non-destructive investigations involved several analytical techniques (IR imaging, UV-Induced Visible Fluorescence, and X-ray Fluorescence analyses) that provided mapping and characterization of pictorial layers and first data about deterioration phenomena. On the basis of this information, a more in-depth study was conducted on micro-fragments aimed at characterizing the stratigraphy and to identify the artist’s technique. Cross-sections were analysed using polarized optical microscopy and electron scanning microscopy coupled with energy-dispersive X-ray spectroscopy to obtain morphological and chemical information on the selected pictorial micro-fragments of the wall painting. The results allowed to characterize the pigments and provide better readability of the whole figure, revealing details that are not visible to the naked eye, important for future historical-artistic and conservative studies. The results represent the first step of a systematic archaeometric research aimed at supporting the ongoing historical-stylistic studies to distinguish the different building phases hypothesized for this religious site which remained buried for three centuries.     

Structure of N-linked oligosaccharides attached to chlorovirus PBCV-1 major capsid protein reveals unusual class of complex N-glycans

The major capsid protein Vp54 from the prototype chlorovirus Paramecium bursaria chlorella virus 1 (PBCV-1) contains four Asn-linked glycans. The structure of the four N-linked oligosaccharides and the type of substitution at each glycosylation site was determined by chemical, spectroscopic, and spectrometric analyses. Vp54 glycosylation is unusual in many ways, including: (i) unlike most viruses, PBCV-1 encodes most, if not all, of the machinery to glycosylate its major capsid protein; (ii) the glycans are attached to the protein by a β-glucose linkage; (iii) the Asn-linked glycans are not located in a typical N-X-(T/S) consensus site; and (iv) the process probably occurs in the cytoplasm. The four glycoforms share a common core structure, and the differences are related to the nonstoichiometric presence of two monosaccharides. The most abundant glycoform consists of nine neutral monosaccharide residues, organized in a highly branched fashion. Among the most distinctive features of the glycoforms are (i) a dimethylated rhamnose as the capping residue of the main chain, (ii) a hyperbranched fucose unit, and (iii) two rhamnose residues with opposite absolute configurations. These glycoforms differ from what has been reported so far in the three domains of life. Considering that chloroviruses and other members of the family Phycodnaviridae may have a long evolutionary history, we suggest that the chlorovirus glycosylation pathway is ancient, possibly existing before the development of the endoplasmic reticulum and Golgi pathway, and involves still unexplored mechanisms.     

Capture–Recapture Method for Estimating Annual Incidence of Imported Dengue,France, 2007–2010

Imported dengue cases pose the public health risk for local circulation in European areas, especially southeast France, where the Aedes mosquito is established. Using a capture–recapture method with Chao’s estimator, we estimated the annual incidence of dengue fever and the completeness of existing mandatory notification and laboratory network surveillance systems. During 2007–2010, >8,300 cases with laboratory evidence of recent dengue infection were diagnosed. Of these cases, 4,500 occurred in 2010, coinciding with intense epidemics in the French West Indies. Over this 4-year period, 327 cases occurred in southeast France during the vector activity period. Of these, 234 cases occurred in 2010, most of them potentially viremic. Completeness of the mandatory notification and laboratory network systems were ≈10% and 40%, respectively, but higher in southeast areas during May–November (32% and 69%, respectively). Dengue surveillance systems in France provide complementary information that is essential to the implementation of control measures.     

Differential effects of glycogen synthase kinase 3 (GSK3) inhibition by lithium or selective inhibitors in the central nervous system

Glycogen synthase kinase (GSK3) is a constitutively active serine-threonine kinase associated to neurological and psychiatric disorders. GSK3 inhibition is considered a mediator of the efficacy of the mood-stabiliser lithium. This study aimed at comparing the central nervous system effect of lithium with the selective GSK3 inhibitors AZ1080 and compound A in biochemical, cellular, and behavioural tests. Collapsin response mediator protein 2 is a neuron-specific GSK3 substrate. Lithium, AZ1080, and compound A inhibited its phosphorylation in rat primary neurons with different pIC₅₀. After systemic treatments with lithium or GSK3 inhibitors to assess specific functional responses, phosphorylation was unchanged in adult rat brain, while it was strongly inhibited by GSK3 inhibitors in pups, differently from lithium. Lithium may exert neurotrophic effect by increasing brain-derived neurotrophic factor (BDNF) levels: in the present experimental conditions, lithium exerted opposite effects on plasma BDNF levels compared to GSK3 inhibitors, suggesting this effect might not be necessarily mediated by GSK3 inhibition alone. While plasma thyroid-stimulating hormone and luteinising hormone were not affected by lithium, they were decreased by selective inhibitors. GH and prolactin displayed similar responses towards reduction. Follicle-stimulating hormone levels were not altered by treatments, whereas melatonin was specifically increased by AZ1080. Lithium impaired mouse spontaneous locomotion and decreased amphetamine-induced hyper-locomotion. AZ1080 had no effects on locomotion, while compound A reduced spontaneous locomotor activity without effects on amphetamine-induced hyper-locomotion. The present results indicate that a broad correlation between the effects of lithium and selective GSK3 inhibitors could not be devised, suggesting alternative mechanisms, whereas overlapping results could be obtained in specific assays.     

The disablement process: Factors associated with progression of disability and recovery in French elderly people

Purpose:?To study the factors associated with progression, recovery and death from different grades of disability in elderly people.

Method:?The sample included 3198 participants of the PAQUID (‘Personnes Agées QUID’) cohort, aged 65 and over and community-dwellers at baseline. Subjects were re-interviewed 1, 3, 5, 8 and 10 years after baseline. A five-state Markov model was used to estimate transition intensities between four grades of disability and toward death. We used a hierarchic scale of disability, which combines basic and instrumental activities of daily living and mobility. Several explanatory variables were investigated: medical, personal and environmental factors.

Results:?The factors associated with progression and/or no recovery of disability were cardiovascular diseases, stroke and diabetes, low cognition, visual impairment and dyspnoea (for pathologies and impairments), older age, female gender, low educational level (for risk factors), depression (for intra-individual factor) and being married, recent hospitalization and number of drugs (for extra-individual factors). Older age, male gender, tobacco consumption and living in an urban area were associated with mortality.

Conclusions:?These findings confirm the independent contribution of each group of variables in the disablement process and stress their different impact on progression of disability or on recovery from different grades of disability.     

Cytochrome P450 2C19 loss-of-function polymorphism is a major determinant of clopidogrel responsiveness in healthy subjects

The capacity of clopidogrel to inhibit ADP-induced platelet aggregation shows wide intersubject variability. To determine whether frequent functional variants of genes coding for candidate cytochrome P450 (CYP) isoenzymes involved in clopidogrel metabolic activation (CYP2C19*2, CYP2B6*5, CYP1A2*1F, and CYP3A5*3 variants) influence the platelet responsiveness to clopidogrel, we conducted a prospective pharmacogenetic study in 28 healthy white male volunteers treated for 7 days with clopidogrel 75 mg/d. We observed that pharmacodynamic response to clopidogrel was significantly associated with the CYP2C19 genotype. Twenty of the subjects were wild-type CYP2C19 (*1/*1) homozygotes, while the other 8 subjects were heterozygous for the loss-of-function polymorphism CYP2C19*2 (*1/*2). Baseline platelet activity was not influenced by the CYP2C19 genotype. In contrast, platelet aggregation in the presence of 10 muM ADP decreased gradually during treatment with clopidogrel 75 mg once daily in *1/*1 subjects, reaching 48.9% +/- 14.9% on day 7 (P < .001 vs baseline), whereas it did not change in *1/*2 subjects (71.8% +/- 14.6% on day 7, P = .22 vs baseline, and P < .003 vs *1/*1 subjects). Similar results were found with VASP phosphorylation. The CYP2C19*2 loss-of-function allele is associated with a marked decrease in platelet responsiveness to clopidogrel in young healthy male volunteers and may therefore be an important genetic contributor to clopidogrel resistance in the clinical setting.