Human epidermal Langerhans cells express the tight junction protein claudin-1 and are present in human genetic claudin-1 deficiency (NISCH syndrome).

Claudin-1 (CLDN1) is a structural tight junction (TJ) protein and is expressed in differentiating keratinocytes and Langerhans cells in the epidermis. Our objective was to identify immunoreactive CLDN1 in human epidermal Langerhans cells and to examine the pattern of epidermal Langerhans cells in genetic human CLDN1 deficiency [neonatal ichthyosis, sclerosing cholangitis (NISCH) syndrome]. Epidermal cells from healthy human skin labelled with CLDN1-specific antibodies were analysed by confocal laser immunofluorescence microscopy and flow cytometry. Skin biopsy sections of two patients with NISCH syndrome were stained with an antibody to CD1a expressed on epidermal Langerhans cells. Epidermal Langerhans cells and a subpopulation of keratinocytes from healthy skin were positive for CLDN1. The gross number and distribution of epidermal Langerhans cells of two patients with molecularly confirmed NISCH syndrome, however, was not grossly altered. Therefore, CLDN1 is unlikely to play a critical role in migration of Langerhans cells (or their precursors) to the epidermis or their positioning within the epidermis. Our findings do not exclude a role of this TJ molecule once Langerhans cells have left the epidermis for draining lymph nodes.

Social network architecture and the maintenance of deleterious cultural traits.

How have changes in communications technology affected the way that misinformation spreads through a population and persists? To what extent do differences in the architecture of social networks affect the spread of misinformation, relative to the rates and rules by which individuals transmit or eliminate different pieces of information (cultural traits)? Here, we use analytical models and individual-based simulations to study how a 'cultural load' of misinformation can be maintained in a population under a balance between social transmission and selective elimination of cultural traits with low intrinsic value. While considerable research has explored how network architecture affects percolation processes, we find that the relative rates at which individuals transmit or eliminate traits can have much more profound impacts on the cultural load than differences in network architecture. In particular, the cultural load is insensitive to correlations between an individual's network degree and rate of elimination when these quantities vary among individuals. Taken together, these results suggest that changes in communications technology may have influenced cultural evolution more strongly through changes in the amount of information flow, rather than the details of who is connected to whom.

Distribution of artifactual gas on post-mortem multidetector computed tomography (MDCT)

L'imagerie est de plus en plus utilisée en médecine forensique. Actuellement, les connaissances nécessaires pour interpréter les images post mortem sont faibles et surtout celles concernant les artéfacts post mortem. Le moyen radiologique le plus utilisé en médecine légale est la tomodensitométrie multi-coupes (TDMC). Un de ses avantages est la détection de gaz dans le corps. Cette technique est utile au diagnostic d'embolie gazeuse mais sa très grande sensibilité rend visible du gaz présent même en petite quantité. Les premières expériences montrent que presque tous les corps scannés présentent du gaz surtout dans le système vasculaire. Pour cette raison, le médecin légiste est confronté à un nouveau problème : la distinction entre du gaz d'origine post-mortem et une embolie gazeuse vraie. Pour parvenir à cette distinction, il est essentiel d'étudier la distribution de ces gaz en post mortem. Aucune étude systématique n'a encore été réalisée à ce jour sur ce sujet.¦Nous avons étudié l'incidence et la distribution des gaz présents en post mortem dans les vaisseaux, dans les os, dans les tissus sous-cutanés, dans l'espace sous-dural ainsi que dans les cavités crânienne, thoracique et abdominale (82 sites au total) de manière à identifier les facteurs qui pourraient distinguer le gaz post-mortem artéfactuel d'une embolie gazeuse¦Les données TDMC de 119 cadavres ont été étudiées rétrospectivement. Les critères d'inclusion des sujets sont l'absence de lésion corporelle permettant la contamination avec l'air extérieur, et, la documentation du délai entre le moment du décès et celui du CT-scan (p.ex. rapport de police, protocole de réanimation ou témoin). La présence de gaz a été évaluée semi-quantitativement par deux radiologues et codifiée. La codification est la suivante : grade 0 = pas de gaz, grade 1 = une à quelques bulles d'air, grade 2 = structure partiellement remplie d'air, grade 3 = structure complètement remplie d'air.¦Soixante-quatre des 119 cadavres présentent du gaz (62,2%), et 56 (75,7%) ont montré du gaz dans le coeur. Du gaz a été détecté le plus fréquemment dans le parenchyme hépatique (40%); le coeur droit (ventricule 38%, atrium 35%), la veine cave inférieure (infra-rénale 30%, supra-rénale 26%), les veines sus-hépatiques (gauche 26%, moyenne 29%, droite 22 %), et les espaces du porte (29%). Nous avons constaté qu'une grande quantité de gaz liée à la putréfaction présente dans le coeur droit (grade 3) est associée à des collections de gaz dans le parenchyme hépatique (sensibilité = 100%, spécificité = 89,7%). Pour décrire nos résultats, nous avons construit une séquence d'animation qui illustre le processus de putréfaction et l'apparition des gaz à la TDMC post-mortem.¦Cette étude est la première à montrer que l'apparition post-mortem des gaz suit un modèle de distribution spécifique. L'association entre la présence de gaz intracardiaque et dans le parenchyme hépatique pourrait permettre de distinguer du gaz artéfactuel d'origine post-mortem d'une embolie gazeuse vraie. Cette étude fournit une clé pour le diagnostic de la mort due à une embolie gazeuse cardiaque sur la base d'une TDMC post-mortem.¦Abstract¦Purpose: We investigated the incidence and distribution of post-mortem gas detected with multidetector computed tomography (MDCT) to identify factors that could distinguish artifactual gas from cardiac air embolism.¦Material and Methods: MDCT data of 119 cadavers were retrospectively examined. Gas was semiquantitatively assessed in selected blood vessels, organs and body spaces (82 total sites).¦Results: Seventy-four of the 119 cadavers displayed gas (62.2%; CI 95% 52.8 to 70.9), and 56 (75.7%) displayed gas in the heart. Most gas was detected in the hepatic parenchyma (40%); right heart (38% ventricle, 35% atrium), inferior vena cava (30% infrarenally, 26% suprarenally), hepatic veins (26% left, 29% middle, 22% right), and portal spaces (29%). Male cadavers displayed gas more frequently than female cadavers. Gas was detected 5-84 h after death; therefore, the post-mortem interval could not reliably predict gas distribution (rho=0.719, p<0.0001). We found that a large amount of putrefaction-generated gas in the right heart was associated with aggregated gas bubbles in the hepatic parenchyma (sensitivity = 100%, specificity = 89.7%). In contrast, gas in the left heart (sensitivity = 41.7%, specificity = 100%) or in peri-umbilical subcutaneous tissues (sensitivity = 50%, specificity = 96.3%) could not predict gas due to putrefaction.¦Conclusion: This study is the first to show that the appearance of post-mortem gas follows a specific distribution pattern. An association between intracardiac gas and hepatic parenchymal gas could distinguish between post- mortem-generated gas and vital air embolism. We propose that this finding provides a key for diagnosing death due to cardiac air embolism.

Etudiants en médecine et centres médico-sociaux: préparer l'avenir [Medical students and community health care centers: preparing the future].

Since 2011, second year medical students from Lausanne University follow a single day course in the community health care centers of the Canton of Vaud. They discover the medico-social network and attend to patients' visits at home. They experience the importance of the information transmission and the partnership between informal caregivers, professional caregivers, general practitioner and hospital units. The goal of this course is to help the future physicians to collaborate with the community health care centers teams. This will be particularly important in the future with an aging and more dependant population.

Higher Risk of Incident Hepatitis C Virus Coinfection Among Men Who Have Sex With Men, in Whom the HIV Genetic Bottleneck at Transmission Was Wide.

BACKGROUND: High-risk sexual behaviors have been suggested as drivers of the recent dramatic increase of sexually transmitted hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). METHODS: We assessed the association between the genetic bottleneck of HIV at transmission and the prevalence and incidence of HCV coinfection in HIV-infected MSM from the Swiss HIV Cohort Study (SHCS). As a proxy for the width of the transmission bottleneck, we used the fraction of ambiguous nucleotides detected by genotypic resistance tests sampled during early HIV infection. We defined a broad bottleneck as a fraction of ambiguous nucleotides exceeding a previously established threshold (0.5%). RESULTS: From the SHCS, we identified 671 MSM with available results of HCV serologic tests and with an HIV genotypic resistance test performed during early HIV infection. Of those, 161 (24.0%) exhibited a broad HIV transmission bottleneck, 38 (5.7%) had at least 1 positive HCV test result, and 26 (3.9%) had an incident HCV infection. Individuals with broad HIV transmission bottlenecks exhibited a 2-fold higher odds of having ever experienced an HCV coinfection (odds ratio, 2.2 [95% confidence interval {CI}, 1.1-4.3]) and a 3-fold higher hazard of having an incident HCV infection (hazard ratio, 3.0 [95% CI, 1.4-6.6]) than individuals with narrow HIV transmission bottlenecks. CONCLUSIONS: Our results indicate that the currently occurring sexual spread of HCV is focused on MSM who are prone to exhibit broad HIV transmission bottlenecks. This is consistent with an important role of high-risk behavior and mucosal barrier impairment in the transmission of HCV among MSM.

Comparative phylogeography and postglacial colonization routes in Europe.

The Quaternary cold periods in Europe are thought to have heavily influenced the amount and distribution of intraspecific genetic variation in both animals and plants. The phylogeographies of 10 taxa, including mammals (Ursus arctos, Sorex spp., Crocidura suaveolens, Arvicola spp.), amphibians (Triturus spp.), arthropods (Chorthippus parallelus), and plants (Abies alba, Picea abies, Fagus sylvatica, Quercus spp.), were analysed to elucidate general trends across Europe. Only a small degree of congruence was found amongst the phylogeographies of the 10 taxa, but the likely postglacial colonization routes exhibit some similarities. A Brooks parsimony analysis produced an unrooted area phylogram, showing that: (i) the northern regions were colonized generally from the Iberic and Balkanic refugia; and (ii) the Italian lineages were often isolated due to the presence of the Alpine barrier. The comparison of colonization routes highlighted four main suture-zones where lineages from the different refugia meet. Some of the intraspecific genetic distances among lineages indicated a prequaternary divergence that cannot be connected to any particular cold period, but are probably related mainly to the date of arrival of each taxon in the European continent. As a consequence, molecular genetics so far appears to be of limited use in dating Quaternary events.

Photoreceptor types and distributions in the retinae of insectivores.

The retinae of insectivores have been rarely studied, and their photoreceptor arrangements and expression patterns of visual pigments are largely unknown. We have determined the presence and distribution of cones in three species of shrews (common shrew Sorex araneus, greater white-toothed shrew Crocidura russula, dark forest shrew Crocidura poensis; Soricidae) and in the lesser hedgehog tenrec Echinops telfairi (Tenrecidae). Special cone types were identified and quantified in flattened whole retinae by antisera/antibodies recognizing the middle-to-long-wavelength-sensitive (M/L-)cone opsin and the short-wavelength-sensitive (S-)cone opsin, respectively. A combination of immunocytochemistry with conventional histology was used to assess rod densities and cone/rod ratios. In all four species the rods dominate at densities of about 230,000-260,000/mm2. M/L- and S-cones are present, comprising between 2% of the photoreceptors in the nocturnal Echinops telfairi and 13% in Sorex araneus that has equal diurnal and nocturnal activity phases. This suggests dichromatic color vision like in many other mammals. A striking feature in all four species are dramatically higher S-cone proportions in ventral than in dorsal retina (0.5% vs. 2.5-12% in Sorex, 5-15% vs. 30-45% in Crocidura poensis, 3-12% vs. 20-50% in Crocidura russula, 10-30% vs. 40-70% in Echinops). The functional and comparative aspects of these structural findings are discussed.

The adjective petit 'small, little' in French acquisition data: an example of the relationship between pragmatics and morphosyntactic development

In French the adjective petit 'small, little' has a special status: it fulfills various pragmatic functions in addition to semantic meanings and it is thus highly frequent in discourse. Résumé: This study, based on the data of two children, aged 1;6 to 2;11, argues that petit and its pragmatic meanings play a specific role in the acquisition of French adjectives. In contrast to what is expected in child language, petit favours the early development of a pattern of noun phrase with prenominal attributive adjective. The emergence and distribution of petit in the children's production is examined and related to its distribution in the input, and the detailed pragmatic meanings and functions of petit are analysed. Prenominal petit emerges early as the preferred and most productive adjective. Pragmatic meanings of petit appear to be predominant in this early age and are of two main types: expressions of endearment (in noun phrases) and mitigating devices whose scope is the entire utterance. These results, as well as instances of children's pragmatic overgeneralizations, provide new evidence that at least some pragmatic meanings are prior to semantic meanings in early acquisition.

Familial occurrence of an association of multiple intestinal atresia and choanal atresia: a new syndrome?

We report on two familial cases from a non-consanguineous marriage, presenting multiple intestinal and choanal atresia. Massive hydramnios and dilatation of the bowel were observed at 29 weeks of gestation during routine ultrasound scan of a healthy mother. The fetal karyotype was normal and cystic fibrosis screening was negative. Regular scans were performed throughout the pregnancy. The child was born at 34 weeks gestation. Choanal atresia was diagnosed at birth and abdominal investigations showed multiple atresia interesting both the small bowel and the colon. Further interventions were necessary because of recurrent obstructions. During the following pregnancy, a dilatation of the fetal intestinal tract was detected by ultrasonography at 27 weeks of gestation. Pregnancy was interrupted. Post-mortem examination of the fetus confirmed the stenosis of long segments of the small intestine associated with areas of colonic atresia. In both cases, histology and distribution were consistent with those reported in hereditary multiple intestinal atresia (HMIA). An association between multiple intestinal and choanal atresia has never been reported. We suggest it could correspond to a new autosomal recessive entity for which cytogenetic investigations and high-resolution array CGH revealed no visible anomalies.

The fixation of the cemented femoral component. Effects of stem stiffness, cement thickness and roughness of the cement-bone surface.

After cemented total hip arthroplasty (THA) there may be failure at either the cement-stem or the cement-bone interface. This results from the occurrence of abnormally high shear and compressive stresses within the cement and excessive relative micromovement. We therefore evaluated micromovement and stress at the cement-bone and cement-stem interfaces for a titanium and a chromium-cobalt stem. The behaviour of both implants was similar and no substantial differences were found in the size and distribution of micromovement on either interface with respect to the stiffness of the stem. Micromovement was minimal with a cement mantle 3 to 4 mm thick but then increased with greater thickness of the cement. Abnormally high micromovement occurred when the cement was thinner than 2 mm and the stem was made of titanium. The relative decrease in surface roughness augmented slipping but decreased debonding at the cement-bone interface. Shear stress at this site did not vary significantly for the different coefficients of cement-bone friction while compressive and hoop stresses within the cement increased slightly.

DuP 532, an angiotensin II receptor antagonist: first administration and comparison with losartan.

We investigated the tolerability and angiotensin II antagonist activity of oral DuP 532 in healthy male subjects. DuP 532 (1 to 200 mg) was well tolerated, with no effect on blood pressure or heart rate. Compared with losartan (100 mg), DuP 532 (200 mg) was a weak antagonist of pressor responses to intravenous angiotensin II. Maximum inhibition of diastolic pressor response was 86% (95% confidence interval [CI], 84%, 88%) approximately 4.6 hours after losartan and 48% (95% CI, 38%, 56%) 8.7 hours after DuP 532. Twenty-four hours after dosing, inhibition by losartan and DuP 532 was similar (40% to 45%). DUP 532 is extensively bound in human plasma, with an in vitro free fraction of 0.06. Although DuP 532 and EXP3174 (losartan's active metabolite) have similar AT1-receptor potency, and plasma concentrations of DuP 532 were much greater than losartan/EXP3174, the level of antagonism was much less for DuP 532. These results indicate that multiple factors determine the in vivo potency of angiotensin II antagonists, including affinity for and distribution to the receptor as modulated by plasma binding.

Structural determinants involved in the activation and regulation of G protein-coupled receptors: lessons from the alpha1-adrenegic receptor subtypes.

The aim of a large number of studies on G protein-coupled receptors was centered on understanding the structural basis of their main functional properties. Here, we will briefly review the results obtained on the alpha1-adrenergic receptor subtypes belonging to the rhodopsin-like family of receptors. These findings contribute, on the one hand, to further understand the molecular basis of adrenergic transmission and, on the other, to provide some generalities on the structure-functional relationship of G protein-coupled receptors.

Organic geochemistry of Jurassic-Cretaceous source rocks and oil seeps from the profile across the Adriatic-Dinaric carbonate platform

Organic geochemical and stable isotope investigations were performed to provide an insight into the depositional environments, origin and maturity of the organic matter in Jurassic and Cretaceous formations of the External Dinarides. A correlation is made among various parameters acquired from Rock-Eval, gas chromatography-mass spectrometry data and isotope analysis of carbonates and kerogen. Three groups of samples were analysed. The first group includes source rocks derived from Lower Jurassic limestone and Upper Jurassic ``Leme'' beds, the second from Upper Cretaceous carbonates, while the third group comprises oil seeps genetically connected with Upper Cretaceous source rocks. The carbon and oxygen isotopic ratios of all the carbonates display marine isotopic composition. Rock-Eval data and maturity parameter values derived from biomarkers define the organic matter of the Upper Cretaceous carbonates as Type I-S and Type II-S kerogen at the low stage of maturity up to entering the oil-generating window. Lower and Upper Jurassic source rocks contain early mature Type III mixed with Type IV organic matter. All Jurassic and Cretaceous potential source rock extracts show similarity in triterpane and sterane distribution. The hopane and sterane distribution pattern of the studied oil seeps correspond to those from Cretaceous source rocks. The difference between Cretaceous oil seeps and potential source rock extracts was found in the intensity and distribution of n-alkanes, as well as in the abundance of asphaltenes which is connected to their biodegradation stage. In the Jurassic and Cretaceous potential source rock samples a mixture of aromatic hydrocarbons with their alkyl derivatives were indicated, whereas in the oil seep samples extracts only asphaltenes were observed.

Long sequence duplications, repeats, and palindromes in HIV-1 gp120: length variation in V4 as the product of misalignment mechanism.

We have shown that indels in gp120 V4 are associated to the presence of duplicated and palindromic sequences, suggesting that they may be produced by strand-slippage misalignment mechanism. Indels in V4 involved region-specific duplications 9 to 15 bp long, and repeats of various lengths, associated to trinucleotides AAT. No duplications were found in V3 and C3. The frequency of palindromic sequences in individual genes was found to be significantly higher in gp120 (p < or = 3.00E-7), and significantly lower in Tat (p < or = 9.00E-7) than the average frequency calculated over the full genome. The finding of elements of misalignment in association with indels in V4 suggests that these mutations may occur in proviral DNA after integration of HIV into the host genome. It also implies that occurrence of large indels in gp120 is not random but is directed by the presence and distribution of elements of misalignment in the HIV genome.

Effects of sample size on the performance of species distribution models

A wide range of modelling algorithms is used by ecologists, conservation practitioners, and others to predict species ranges from point locality data. Unfortunately, the amount of data available is limited for many taxa and regions, making it essential to quantify the sensitivity of these algorithms to sample size. This is the first study to address this need by rigorously evaluating a broad suite of algorithms with independent presence-absence data from multiple species and regions. We evaluated predictions from 12 algorithms for 46 species (from six different regions of the world) at three sample sizes (100, 30, and 10 records). We used data from natural history collections to run the models, and evaluated the quality of model predictions with area under the receiver operating characteristic curve (AUC). With decreasing sample size, model accuracy decreased and variability increased across species and between models. Novel modelling methods that incorporate both interactions between predictor variables and complex response shapes (i.e. GBM, MARS-INT, BRUTO) performed better than most methods at large sample sizes but not at the smallest sample sizes. Other algorithms were much less sensitive to sample size, including an algorithm based on maximum entropy (MAXENT) that had among the best predictive power across all sample sizes. Relative to other algorithms, a distance metric algorithm (DOMAIN) and a genetic algorithm (OM-GARP) had intermediate performance at the largest sample size and among the best performance at the lowest sample size. No algorithm predicted consistently well with small sample size (n < 30) and this should encourage highly conservative use of predictions based on small sample size and restrict their use to exploratory modelling.