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Rasd2 is a striatal GTP-binding protein that modulates Akt and mTOR signaling cascades, well known to be highly vulnerable pathways in psychiatric disorders.
We investigated the association of Rasd2 and its genetic variation with a series of prefronto-striatal phenotypes related to psychosis in rodents and humans.
We want to provide evidence that Rasd2 controls the vulnerability to schizophrenia-related behavior induced by psychothomimetic drugs in mice. Moreover, we aim to find genetic variations within the Rasd2 gene that influence a series of brain schizophrenia-related phenotypes in human.
Rasd2 knockout mice were employed to evaluate schizophrenia-like behaviors induced by psychotomimetic drugs like amphetamine and phencyclidine. Furthermore, we investigated if RASD2genetic variations in humans are associated with mRNA expression in post-mortem prefrontal cortex, as well as prefrontal and striatal grey matter volume and physiology during working memory as measured with MRI in healthy subjects. Finally, we assessed RASD2mRNA expression levels in post-mortem brains of patients with schizophrenia and bipolar disorder.
We found that both psychotomimetics triggered greater vulnerability to motor stimulation and to prepulse inhibition deficits in Rasd2 mutants. In humans, we found that a genetic variation (rs6518956) within RASD2 predicts prefrontal mRNA expression as well as prefrontal grey matter volume and prefronto-striatal activity during working memory. Finally, we reported that RASD2 mRNA expression is slightly reduced in post-mortem prefrontal cortex of patients with schizophrenia.
Collectively, our data suggests that RASD2represents a gene of potential interest in psychiatric disorders for its ability to modulate prefronto-striatal phenotypes related to schizophrenia.
D-aspartate (D-Asp) is an atypical amino acid that binds to and activates NMDARs. D-Asp occurs abundantly in the embryonic brain of mammals and rapidly decreases after birth, due to the activity of the enzyme D-Aspartate Oxidase (DDO). The agonistic activity of D-Asp on NMDARs and its neurodevelopmental occurrence make this D-amino acid a potential mediator for NMDAR-related alterations observed in schizophrenia. Consistently, substantial reduction of D-Asp was observed in post-mortem schizophrenia brains.
We evaluated the potential contribution of D-Asp as neurodevelopmental modulator of brain circuits and behaviors relevant to schizophrenia.
We analyzed DDO mRNA expression in the post-mortem prefrontal cortex of schizophrenic patients. Moreover, we treated knockout mice for Ddo gene (Ddo-/-) with the NMDAR antagonist phencyclidine to evaluate their schizophrenia-relevant behaviors and circuits. Finally, we assessed cortico-hippocampal connectivity of these mice.
DDO mRNA detection was performed by quantitative PCR. Phencyclidine-induced schizophrenia-like behaviours were assessed through motor activity and prepulse inhibition paradigms. Resting-state and pharmacological fMRI were used to evaluate functional circuits and connectivity.
DDO mRNA expression is increased in frontal samples of schizophrenic patients. In mice, the absence of Ddo gene produces a significant reduction in phencyclidine-induced motor hyper-activity and prepulse inhibition deficit. Furthermore, increased levels of D-Asp in Ddo-/- animals significantly inhibit functional circuits activated by phencyclidine, and affect the development of cortico-hippocampal connectivity networks potentially involved in schizophrenia.
Our data suggest that D-Asp, through the regulation exerted by DDO, may have a role in the pathophysiology of schizophrenia.
The aim of this study was to describe the incidence and risk factors for respiratory morbidity during the 12-month period following the first respiratory syncytial virus (RSV) season in 242 preterm infants [<33 weeks gestational age (GA)] without bronchopulmonary dysplasia and 201 full-term infants (39–41 weeks GA) from the French CASTOR study cohort. Preterm infants had increased respiratory morbidity during the follow-up period compared to full-terms; they were more likely to have wheezing (21% vs. 11%, P = 0·007) and recurrent wheezing episodes (4% vs. 1%, P = 0·049). The 17 infants (14 preterms, three full-terms) who had been hospitalized for RSV-confirmed bronchiolitis during their first RSV season had significantly more wheezing episodes during the follow-up period than subjects who had not been hospitalized for RSV-confirmed bronchiolitis (odds ratio 4·72, 95% confidence interval 1·71–13·08, P = 0·003). Male gender, birth weight <3330 g and hospitalization for RSV bronchiolitis during the infant's first RSV season were independent risk factors for the development of wheezing episodes during the subsequent 12-month follow-up period.
This study was conducted during the 2008–2009 respiratory syncytial virus (RSV) season in France to compare hospitalization rates for bronchiolitis (RSV-confirmed and all types) between very preterm infants (<33 weeks' gestational age, WGA) without bronchopulmonary dysplasia and full-term infants (39–41 WGA) matched for date of birth, gender and birth location, and to evaluate the country-specific risk factors for bronchiolitis hospitalization. Data on hospitalizations were collected both retrospectively and prospectively for 498 matched infants (249 per group) aged <6 months at the beginning of the RSV season. Compared to full-term infants, preterm infants had a fourfold [95% confidence interval (CI) 1·36–11·80] and a sevenfold (95% CI 2·79–17·57) higher risk of being hospitalized for bronchiolitis, RSV-confirmed and all types, respectively. Prematurity was the only factor that significantly increased the risk of being hospitalized for bronchiolitis. The risk of multiple hospitalizations for bronchiolitis in the same infant significantly increased with male gender and the presence of siblings aged ⩾2 years.
Using waste materials as aggregate for new concrete production is a growing tendency, because of several environmental problems. Recycled coarse aggregate (RCA) obtained from crushing waste concrete has lower density and greater absorption than natural aggregate, because of the higher porosity of the mortar attached to the RCA particles. Compressive strength level achieved in recycled concrete may be similar to that of conventional concrete. On the other hand, durable performance of recycled concrete is variable, and diverse evidence can be found in literature for different durability issues. In this paper, chloride ingress in conventional and recycled concrete, made with quartzite aggregate and blended Portland cement is evaluated when immersed in NaCl solution. Two strength levels (21 and 35 MPa) and two contents of RCA (25 and 75%), as substitute of natural quartzite aggregate, were considered. The chloride diffusion coefficient and the relationship between water-soluble chloride and bound chloride are analyzed.
The primary aim of the present study was to determine the survival rates and identify predictors of disease duration in a cohort of Huntington's disease (HD) patients from Southern Italy.
All medical records of HD patients followed between 1977 and 2008 at the Department of Neurological Sciences of Federico II University in Naples were retrospectively reviewed and 135 patients were enrolled in the analysis. At the time of data collection, 41 patients were deceased (19 males and 22 females) with a mean ± SD age at death of 56.6 ± 14.9 years (range 18-83).
The median survival time was 20 years (95% CI: 18.3-21.7). Cox regression analysis showed that the number of CAG in the expanded allele (HR 1.09 for 1 point triplet increase, p=0.002) and age of onset (HR 1.05 for 1 point year increase, p=0.022) were independent and significant predictors of lower survival rates.
We believe that these findings are important for a better understanding of the natural history of the disease and may be relevant in designing future therapeutic trials.
This paper deals with several concrete properties and to what extent they are influenced by slag and limestone filler, either one or both of them are included. Concrete was designed for low paste content, this is, a water reducing admixture (WR) was used to limit mixing water content. The results are compared with concrete made with commercial composite cement, blended during milling. Concrete was tested for compressive strength, sorptivity, resistivity, and water penetration under pressure. The volume of paste in all concrete mixes was the same.
Results showed the effect of slag on concrete transport properties. The effect of limestone filler was minimal either admixed solely or in conjunction with slag. On the other hand, blended cement appeared to be less effective on improving concrete transport properties. Compressive strength was less affected than transport properties by slag inclusion.
The simulation of multiphase flows is an outstanding challenge, due to the inherent complexity of the underlying physical phenomena and to the fact that multiphase flows are very diverse in nature, and so are the laws governing their dynamics. In the last two decades, a new class of mesoscopic methods, based on minimal lattice formulation of Boltzmann kinetic equation, has gained significant interest as an efficient alternative to continuum methods based on the discretisation of the NS equations for non ideal fluids. In this paper, three different multiphase models based on the lattice Boltzmann method (LBM) are discussed, in order to assess the capability of the method to deal with multiphase flows on a wide spectrum of operating conditions and multiphase phenomena. In particular, the range of application of each method is highlighted and its effectiveness is qualitatively assessed through comparison with numerical and experimental literature data.
Λ cold-dark-matter hierarchical models of galaxy formation suggest that the halo of the Milky Way (MW) has been assembled, at least in part, through accretion of protogalactic fragments partially resembling the present-day dwarf spheroidal (dSph) satellites of the MW. Investigation of the stellar populations of the MW's globular clusters (GCs) and dSph companions can thus provide excellent tests to infer the dominant Galaxy-formation scenario, whether merger/accretion or cloud collapse. Pulsating variable stars offer a very powerful tool in this context, since variables of different types allow tracing the different stellar generations in a galaxy and to reconstruct the galaxy's star-formation history and assembly back to the first epochs of galaxy formation. In particular, the RR Lyrae stars, belonging to the old population (t > 10 Gyr), witnessed the epoch of halo formation, and thus hold a crucial role to identify the MW satellites that may have contributed to build up the Galactic halo. In the MW, most GCs with an RR Lyrae population sharply divide into two distinct groups (Oosterhoff types I and II) based on the mean periods and relative proportion of fundamental-mode (RRab) and first-overtone (RRc) RR Lyrae stars. On the other hand, the Galactic-halo field RR Lyrae stars show a dominance of Oosterhoff I properties. Here, we investigate the Oosterhoff properties of a number of different stellar systems, starting from relatively undisturbed dwarf galaxies (the Fornax dSph and its globular clusters), through distorted and tidally disrupting ones (the Bootes and Canes Venatici II dSphs), to possible final relics of the disruption process (the Galactic globular cluster NGC 2419). We are addressing the crucial question of whether the RR Lyrae pulsation properties in these systems conform to the Oosterhoff dichotomy characterizing the MW variables. If they do not, the Galaxy's halo cannot have been assembled by dSph-like protogalactic fragments resembling the present-day dSph companions of the MW. We have reduced and combined long time series from different telescopes, both ground- and space-based. Variable stars have been detected with image-subtraction techniques using the package isis2.1. Periods, amplitudes and Oosterhoff type for all variable stars, as well as color–magnitude diagrams of the stellar populations are discussed for each stellar cluster analyzed.
We have combined B, V, I time-series photometry from three different telescopes (SUBARU, TNG and HST) to study the variable star population of the remote Galactic globular cluster NGC 2419 and derive hints on a possible extragalactic origin for this cluster. We have discovered 40 new variables (34 RR Lyrae stars, 3 SX Phoenicis stars, Scuti 1 eclipsing binary system and 2 red irregular variables) doubling the number of known variable stars in NGC 2419.
The cervico-oculo-acoustic syndrome comprises Klippel-Feil anomaly, sensorineural deafness and Duane's retraction syndrome. Polygenic, autosomal dominant, and X-linked inheritance have been hypothesized. The disorder has rarely been reported in males.
A 42-year-old male, born of consanguineous parents, presented with Duane's syndrome, mixed hearing loss, C2-C3 fusion, neck stiffness, and right facial palsy. A variety of cardiac, neurological and urogenital anomalies occurred in his relatives. The electro-oculographic studies showed impaired abduction and adduction of the right eye and impaired abduction of the left eye. Vergence, vertical eye movements and peripheral vestibular responses were normal. Somatosensory evoked potentials showed absence of the N13 peak and brainstem auditory evoked potentials bilateral delay of the I-III interpeak latencies.
Consanguinity of the patient's parents, not previously reported, suggests autosomal recessive inheritance, but autosomal dominant inheritance is indicated by the family history. The pattern of the oculomotor deficit is consistent with bilateral dysplasia of the abducens nuclei with preserved internuclear neurons in the right abducens nucleus. Neurophysiological investigations revealed lower brainstem and cervical cord involvement.
This paper reports findings from a European Commission funded study of future long-term care expenditure in Germany, Italy, Spain and the United Kingdom, and presents projections of future long-term care expenditure in the four countries under a number of assumptions about the future. Macro-simulation (or cell-based) models were used to make comparable projections based on a set of common assumptions. A central base-case served as a point of comparison by which to explore the sensitivity of the models to alternative scenarios for the key determinants. The sensitivity of the models to variant assumptions about the future numbers of older people, the prevalence of functional dependency and informal care, patterns of long-term provision, and macroeconomic conditions are examined. It was found that, under the base-case, the proportion of gross domestic product spent on long-term care is projected to more than double between 2000 and 2050 in each country. The projected future demand for long-term care services for older people is sensitive to assumptions about the future number of older people, the prevalence of dependency and the availability of informal care, and projected expenditure is sensitive to assumptions about rises in the real unit-costs of services and the structure of the models. It is important, for planning purposes, to recognise the considerable uncertainty about future levels of long-term care expenditure.
Measuring the toughness of brittle coatings has always been a difficult task. Coatings are often too thin to easily prepare a freestanding sample of a defined geometry to use standard toughness measuring techniques. Using standard indentation techniques gives results influenced by the effect of the substrate. A new technique for measuring the toughness of coatings is described here. A precracked micro-beam was produced using focused ion beam (FIB) machining, then imaged and loaded to fracture using a nanoindenter.