Developmental critical period in gentic redox dysregulation: animal and human studies in schizophrenia

Converging evidence favors an abnormal susceptibility to oxidative stress in schizophrenia. Decreased levels of glutathione (GSH), the major cellular antioxidant and redox regulator, was observed in cerebrospinal-fluid and prefrontal cortex of patients. Importantly, abnormal GSH synthesis of genetic origin was observed: Two case-control studies showed an association with a GAG trinucleotide repeat (TNR) polymorphism in the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) catalytic subunit (GCLC) gene. The most common TNR genotype 7/7 was more frequent in controls, whereas the rarest TNR genotype 8/8 was three times more frequent in patients. The disease associated genotypes (35% of patients) correlated with decreased GCLC protein, GCL activity and GSH content. Similar GSH system anomalies were observed in early psychosis patients. Such redox dysregulation combined with environmental stressors at specific developmental stages could underlie structural and functional connectivity anomalies. In pharmacological and knock-out (KO) models, GSH deficit induces anomalies analogous to those reported in patients. (a) morphology: spine density and GABA-parvalbumine immunoreactivity (PV-I) were decreased in anterior cingulate cortex. KO mice showed delayed cortical PV-I at PD10. This effect is exacerbated in mice with increased DA from PD5-10. KO mice exhibit cortical impairment in myelin and perineuronal net known to modulate PV connectivity. (b) physiology: In cultured neurons, NMDA response are depressed by D2 activation. In hippocampus, NMDA-dependent synaptic plasticity is impaired and kainate induced g-oscillations are reduced in parallel to PV-I. (c) cognition: low GSH models show increased sensitivity to stress, hyperactivity, abnormal object recognition, olfactory integration and social behavior. In a clinical study, GSH precursor N-acetyl cysteine (NAC) as add on therapy, improves the negative symptoms and decreases the side effects of antipsychotics. In an auditory oddball paradigm, NAC improves the mismatched negativity, an evoked potential related to pre-attention and to NMDA receptors function. In summary, clinical and experimental evidence converge to demonstrate that a genetically induced dysregulation of GSH synthesis combined with environmental insults in early development represent a major risk factor contributing to the development of schizophrenia Conclusion Based on these data, we proposed a model for PSIP1 promoter activity involving a complex interplay between yet undefined regulatory elements to modulate gene expression.

The identification of two Trypanosoma cruzi I genotypes from domestic and sylvatic transmission cycles in Colombia based on a single polymerase chain reaction amplification of the spliced-leader intergenic region

A single polymerase chain reaction (PCR) reaction targeting the spliced-leader intergenic region of Trypanosoma cruzi I was standardised by amplifying a 231 bp fragment in domestic (TcIDOM) strains or clones and 450 and 550 bp fragments in sylvatic strains or clones. This reaction was validated using 44 blind coded samples and 184 non-coded T. cruzi I clones isolated from sylvatic triatomines and the correspondence between the amplified fragments and their domestic or sylvatic origin was determined. Six of the nine strains isolated from acute cases suspected of oral infection had the sylvatic T. cruzi I profile. These results confirmed that the sylvatic T. cruzi I genotype is linked to cases of oral Chagas disease in Colombia. We therefore propose the use of this novel PCR reaction in strains or clones previously characterised as T. cruziI to distinguish TcIDOMfrom sylvatic genotypes in studies of transmission dynamics, including the verification of population selection within hosts or detection of the frequency of mixed infections by both T. cruzi I genotypes in Colombia.

Nouveautés en médecine interne hospitalière 2007: perspective des chefs de clinique [Highlights 2007 in hospital-based internal medicine: the point of view from the chief residents]

L'année 2007 a été marquée par la publication de plusieurs études internationales concernant directement le quotidien de l'interniste hospitalier. Un résumé de ces travaux ne saurait être qu'un extrait condensé et forcément subjectif d'une croissante et dynamique diversité. Au gré de leurs lectures, de leurs intérêts et de leurs interrogations, les chefs de clinique du Service de médecine interne vous proposent ainsi un parcours original revisitant les thèmes de l'insuffisance cardiaque, du diabète, de l'endocardite, de la BPCO ou de la qualité des soins. Cette variété de sujets illustre à la fois le vaste champ couvert par la médecine interne actuelle, ainsi que les nombreuses incertitudes liées à la pratique médicale moderne basée sur les preuves. In 2007, several international studies brought useful information for the daily work of internists in hospital settings. This summary is of course subjective but reflects the interests and questions of the chief residents of the Department of internal medicine who wrote this article like an original trip in medical literature. This trip will allow you to review some aspects of important fields such as heart failure, diabetes, endocarditis, COPD, and quality of care. Besides the growing diversity of the fields covered by internal medicine, these various topics underline also the uncertainty internists have to face in a practice directed towards evidence.

Studies in stoichiometry with compositional data

Geochemical data that is derived from the whole or partial analysis of various geologic materialsrepresent a composition of mineralogies or solute species. Minerals are composed of structuredrelationships between cations and anions which, through atomic and molecular forces, keep the elementsbound in specific configurations. The chemical compositions of minerals have specific relationships thatare governed by these molecular controls. In the case of olivine, there is a well-defined relationshipbetween Mn-Fe-Mg with Si. Balances between the principal elements defining olivine composition andother significant constituents in the composition (Al, Ti) have been defined, resulting in a near-linearrelationship between the logarithmic relative proportion of Si versus (MgMnFe) and Mg versus (MnFe),which is typically described but poorly illustrated in the simplex.The present contribution corresponds to ongoing research, which attempts to relate stoichiometry andgeochemical data using compositional geometry. We describe here the approach by which stoichiometricrelationships based on mineralogical constraints can be accounted for in the space of simplicialcoordinates using olivines as an example. Further examples for other mineral types (plagioclases andmore complex minerals such as clays) are needed. Issues that remain to be dealt with include thereduction of a bulk chemical composition of a rock comprised of several minerals from which appropriatebalances can be used to describe the composition in a realistic mineralogical framework. The overallobjective of our research is to answer the question: In the cases where the mineralogy is unknown, arethere suitable proxies that can be substituted?Kew words: Aitchison geometry, balances, mineral composition, oxides

Acoustic transport of charge and spins in GaAs-based heterostructures

Report for the scientific sojourn carried out at the Paul Drude Institut für Festkörperelektronik of the Stanford University, USA, from 2010 to 2012. The objective of this project is the transport and control of electronic charge and spin along GaAs-based semiconductor heterostructures. The electronic transport has been achieved by taking advantage of the piezolectric field induced by surface acoustic waves in non-centrosymmetric materials like GaAs. This piezolectric field separates photogenerated electrons and holes at different positions along the acoustic wave, where they acummulate and are transported at the same velocity as the wave. Two different kinds of structures have been studied: quantum wells grown along the (110) direction, both intrinsic and n-doped, as well as GaAs nanowires. The analysis of the charge acoustic transport was performed by micro-photoluminescence, whereas the detection of the spin transport was done either by analyzing the polarization state of the emitted photoluminescence or by Kerr reflectometry. Our results in GaAs quantum wells show that charge and spin transport is clearly observed at the non-doped structures,obtaining spin lifetimes of the order of several nanoseconds, whereas no acoutically induced spin transport was detected for the n-doped quantum wells. In the GaAs nanowires, we were able of transporting successfully both electrons and holes along the nanowire axis, but no conservation of the spin polarization has been observed until now. The photoluminescence emitted by these structures after acoustic transport, however, shows anti-bunching characteristics, making this system a very good candidate for its use as single photon emitters.

How are "teaching the teachers" courses in evidence based medicine evaluated? A systematic review.

BACKGROUND: Teaching of evidence-based medicine (EBM) has become widespread in medical education. Teaching the teachers (TTT) courses address the increased teaching demand and the need to improve effectiveness of EBM teaching. We conducted a systematic review of assessment tools for EBM TTT courses.To summarise and appraise existing assessment methods for teaching the teachers courses in EBM by a systematic review. METHODS: We searched PubMed, BioMed, EmBase, Cochrane and Eric databases without language restrictions and included articles that assessed its participants. Study selection and data extraction were conducted independently by two reviewers. RESULTS: Of 1230 potentially relevant studies, five papers met the selection criteria. There were no specific assessment tools for evaluating effectiveness of EBM TTT courses. Some of the material available might be useful in initiating the development of such an assessment tool. CONCLUSION: There is a need for the development of educationally sound assessment tools for teaching the teachers courses in EBM, without which it would be impossible to ascertain if such courses have the desired effect.

Raman scattering of InSb quantum dots grown on InP substrates

In this paper we present the Raman scattering of self-assembled InSb dots grown on (001) oriented InP substrates. The samples were grown by pulsed molecular beam epitaxy mode. Two types of samples have been investigated. In one type the InSb dots were capped with 200 monolayers of InP; in the other type no capping was deposited after the InSb dot formation. We observe two peaks in the Raman spectra of the uncapped dot, while only one peak is observed in the Raman spectra of the capped dots. In the case of the uncapped dots the peaks are attributed to LO-like and TO-like vibration of completely relaxed InSb dots, in agreement with high resolution transmission electron microscopy photographs. The Raman spectra of the capped dot suggest a different strain state in the dot due to the capping layer.

Myélite transverse et neuromyélite optique chez l'enfant. A propos de trois observations [Transverse myelitis and optic neuromyelitis in children. Apropos of 3 case reports]

We report on three children with acute transverse myelitis. One of them also had optic neuritis. In connection with these three cases, we discuss etiology, diagnosis and outcome of transverse myelitis in childhood and possible involvement of the optic nerve. Our observations show the variability of spinal cord deficit and the fact that there can be a good prognosis, despite severe initial neurological deficits and massive elevation of basic myelin protein in children with ATM.

Systematics of properties of the electron gas in deep-etched quantum wires

An efficient method is developed for an iterative solution of the Poisson and Schro¿dinger equations, which allows systematic studies of the properties of the electron gas in linear deep-etched quantum wires. A much simpler two-dimensional (2D) approximation is developed that accurately reproduces the results of the 3D calculations. A 2D Thomas-Fermi approximation is then derived, and shown to give a good account of average properties. Further, we prove that an analytic form due to Shikin et al. is a good approximation to the electron density given by the self-consistent methods.

Prevalence of hypertension in schoolchildren based on repeated measurements and association with overweight.

OBJECTIVE: Most studies assess the prevalence of hypertension in pediatric populations based on blood pressure (BP) readings taken on a single visit. We determined the prevalence of hypertension measured on up to three visits in a Swiss pediatric population and examined the association between hypertension and overweight and selected other factors. METHODS: Anthropometric data and BP were measured in all children of the sixth school grade of the Vaud canton (Switzerland) in 2005-2006. 'Elevated BP' was defined according to sex-specific, age-specific and height-specific US reference data. BP was measured on up to two additional visits in children with elevated BP. 'Hypertension' was defined as 'elevated BP' on all three visits. RESULTS: Out of 6873 children, 5207 (76%) participated [2621 boys, 2586 girls; mean (SD) age, 12.3 (0.5) years]. The prevalence of elevated BP was 11.4, 3.8 and 2.2% on first, second and thirds visits, respectively; hence 2.2% had hypertension. Among hypertensive children, 81% had isolated systolic hypertension. Hypertension was associated with excess body weight, elevated heart rate and parents' history of hypertension. Of the children, 16.1% of boys and 12.4% of girls were overweight or obese (CDC criteria, body mass index >or= 85th percentile). Thirty-seven percent of cases of hypertension could be attributed to overweight or obesity. CONCLUSIONS: The proportion of children with elevated BP based on one visit was five times higher than based on three measurements taken at few-week intervals. Our data re-emphasize the need for prevention and control of overweight in children to curb the global hypertension burden.

Effect of the MC1R gene on sexual dimorphism in melanin-based colorations.

Variants of the melanocortin-1 receptor (MC1R) gene result in abrupt, naturally selected colour morphs. These genetic variants may differentially affect sexual dimorphism if one morph is naturally selected in the two sexes but another morph is naturally or sexually selected only in one of the two sexes (e.g. to confer camouflage in reproductive females or confer mating advantage in males). Therefore, the balance between natural and sexual selections can differ between MC1R variants, as suggest studies showing interspecific correlations between sexual dimorphism and the rate of nonsynonymous vs. synonymous amino acid substitutions at the MC1R. Surprisingly, how MC1R is related to within-species sexual dimorphism, and thereby to sex-specific selection, has not yet been investigated. We tackled this issue in the barn owl (Tyto alba), a species showing pronounced variation in the degree of reddish pheomelanin-based coloration and in the number and size of black feather spots. We found that a valine (V)-to-isoleucine (I) substitution at position 126 explains up to 30% of the variation in the three melanin-based colour traits and in feather melanin content. Interestingly, MC1R genotypes also differed in the degree of sexual colour dimorphism, with individuals homozygous for the II MC1R variant being 2 times redder and 2.5 times less sexually dimorphic than homozygous individuals for the VV MC1R variant. These findings support that MC1R interacts with the expression of sexual dimorphism and suggest that a gene with major phenotypic effects and weakly influenced by variation in body condition can participate in sex-specific selection processes.

Optoelectronic studies in nanocrystalline silicon Schottky diodes obtained by Hot-Wire Chemical Vapour Deposition

The very usual columnar growth of nanocrystalline silicon leads to electronic transport anisotropies. Whereas electrical measurements with coplanar electrodes only provide information about the electronic transport parallel to the substrate, it is the transverse transport which determines the collection efficiency in thin film solar cells. Hence, Schottky diodes on transparent electrodes were obtained by hot-wire CVD in order to perform external quantum efficiency and surface photovoltage studies in sandwich configuration. These measurements allowed to calculate a transverse collection length, which must correlate with the photovoltaic performance of thin film solar cells. Furthermore, the density of charge trapped at localized states in the bandgap was estimated from the voltage dependence of the depletion capacitance of these rectifying contacts.

Advances in MRI-based computational neuroanatomy: from morphometry to in-vivo histology.

PURPOSE OF REVIEW: Current computational neuroanatomy based on MRI focuses on morphological measures of the brain. We present recent methodological developments in quantitative MRI (qMRI) that provide standardized measures of the brain, which go beyond morphology. We show how biophysical modelling of qMRI data can provide quantitative histological measures of brain tissue, leading to the emerging field of in-vivo histology using MRI (hMRI). RECENT FINDINGS: qMRI has greatly improved the sensitivity and specificity of computational neuroanatomy studies. qMRI metrics can also be used as direct indicators of the mechanisms driving observed morphological findings. For hMRI, biophysical models of the MRI signal are being developed to directly access histological information such as cortical myelination, axonal diameters or axonal g-ratio in white matter. Emerging results indicate promising prospects for the combined study of brain microstructure and function. SUMMARY: Non-invasive brain tissue characterization using qMRI or hMRI has significant implications for both research and clinics. Both approaches improve comparability across sites and time points, facilitating multicentre/longitudinal studies and standardized diagnostics. hMRI is expected to shed new light on the relationship between brain microstructure, function and behaviour, both in health and disease, and become an indispensable addition to computational neuroanatomy.

Condition-dependence, pleiotropy and the handicap principle of sexual selection in melanin-based colouration.

The signalling function of melanin-based colouration is debated. Sexual selection theory states that ornaments should be costly to produce, maintain, wear or display to signal quality honestly to potential mates or competitors. An increasing number of studies supports the hypothesis that the degree of melanism covaries with aspects of body condition (e.g. body mass or immunity), which has contributed to change the initial perception that melanin-based colour ornaments entail no costs. Indeed, the expression of many (but not all) melanin-based colour traits is weakly sensitive to the environment but strongly heritable suggesting that these colour traits are relatively cheap to produce and maintain, thus raising the question of how such colour traits could signal quality honestly. Here I review the production, maintenance and wearing/displaying costs that can generate a correlation between melanin-based colouration and body condition, and consider other evolutionary mechanisms that can also lead to covariation between colour and body condition. Because genes controlling melanic traits can affect numerous phenotypic traits, pleiotropy could also explain a linkage between body condition and colouration. Pleiotropy may result in differently coloured individuals signalling different aspects of quality that are maintained by frequency-dependent selection or local adaptation. Colouration may therefore not signal absolute quality to potential mates or competitors (e.g. dark males may not achieve a higher fitness than pale males); otherwise genetic variation would be rapidly depleted by directional selection. As a consequence, selection on heritable melanin-based colouration may not always be directional, but mate choice may be conditional to environmental conditions (i.e. context-dependent sexual selection). Despite the interest of evolutionary biologists in the adaptive value of melanin-based colouration, its actual role in sexual selection is still poorly understood.

Brain imaging studies in severe somatization

Somatization was described 4000 years ago but the pathophysiology of the, phenomenon is unknown. The aim of this investigation was to explore whether central nervous system (CNS) pathology is associated with severe somatization which was operationalized as somatization disorder (SD) and undifferentiated somatoform disorder. The study sample consisted of severely somatizing people who were included into the study after a multi-phase screening procedure in order to exclude psychiatric comorbidities and physical illnesses. Diagnosis of somatization disorder or undifferentiated sofatoform disorder were set according to Diagnostic and Statistical Manual of Mental Disorders 4th ed. (DSM-IV). The first study explored the regional cerebral metabolic rate of glucose (rCMRGlc) in severely somatizing females and found it to be reduced in several regions of the brain compared to healthy controls. The second study observed brain morphology with magnetic resonance imaging (MRI) based on the findings from the first study and showed enlarged caudate nuclei in somatizing women compared to healthy volunteers. The third study investigated temperament factors and brain metabolism, and their association with severe somatization. Low caudate and putamen metabolism, low novelty seeking as well as high harm avoidance were found to be associated with severe somatization in women, reduced caudate metabolism having the strongest association. The last study is a report of man with left-side gradient of multiple symptoms of unknown origin in the body. The examination revealed a hypermetabolic nucleus putamen on the contralateral side. All the main results reported in these four articles are original findings. The results suggest that CNS pathology is involved in the pathophysiology of severe somatization.