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1.
Opt Express ; 25(15): 16957-16970, 2017 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-28789195

RESUMEN

The Petawatt Aquitaine Laser (PETAL) facility was designed and constructed by the French Commissariat à l'énergie atomique et aux énergies alternatives (CEA) as an additional PW beamline to the Laser MegaJoule (LMJ) facility. PETAL energy is limited to 1 kJ at the beginning due to the damage threshold of the final optics. In this paper, we present the commissioning of the PW PETAL beamline. The first kJ shots in the amplifier section with a large spectrum front end, the alignment of the synthetic aperture compression stage and the initial demonstration of the 1.15 PW @ 850 J operations in the compression stage are detailed. Issues encountered relating to damage to optics are also addressed.

2.
Mol Psychiatry ; 22(6): 874-883, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-27113998

RESUMEN

A recent genome-wide association meta-analysis for Alzheimer's disease (AD) identified 19 risk loci (in addition to APOE) in which the functional genes are unknown. Using Drosophila, we screened 296 constructs targeting orthologs of 54 candidate risk genes within these loci for their ability to modify Tau neurotoxicity by quantifying the size of >6000 eyes. Besides Drosophila Amph (ortholog of BIN1), which we previously implicated in Tau pathology, we identified p130CAS (CASS4), Eph (EPHA1), Fak (PTK2B) and Rab3-GEF (MADD) as Tau toxicity modulators. Of these, the focal adhesion kinase Fak behaved as a strong Tau toxicity suppressor in both the eye and an independent focal adhesion-related wing blister assay. Accordingly, the human Tau and PTK2B proteins biochemically interacted in vitro and PTK2B co-localized with hyperphosphorylated and oligomeric Tau in progressive pathological stages in the brains of AD patients and transgenic Tau mice. These data indicate that PTK2B acts as an early marker and in vivo modulator of Tau toxicity.


Asunto(s)
Quinasa 2 de Adhesión Focal/genética , Proteínas tau/metabolismo , Enfermedad de Alzheimer/genética , Animales , Biomarcadores , Modelos Animales de Enfermedad , Drosophila/genética , Quinasa 2 de Adhesión Focal/metabolismo , Sitios Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Humanos , Factores de Riesgo , Proteínas tau/genética
3.
Ticks Tick Borne Dis ; 7(5): 644-652, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26897396

RESUMEN

Lyme borreliosis is a major zoonosis in Europe, with estimates of over 26,000 cases per year in France alone. The etiological agents are spirochete bacteria that belong to the Borrelia burgdorferi sensu lato (s. l.) complex and are transmitted by hard ticks among a large range of vertebrate hosts. In Europe, the tick Ixodes ricinus is the main vector. In the absence of a vaccine and given the current difficulties to diagnose and treat chronic Lyme syndromes, there is urgent need for prevention. In this context, accurate information on the spatial patterns of risk of exposure to ticks is of prime importance for public health. The objective of our study was to provide a snapshot map of the risk of human infection with B. burgdorferi s. l. pathogens in a periurban forest at a high resolution, and to analyze the factors that contribute to variation in this risk. Field monitoring took place over three weeks in May 2011 in the suburban Sénart forest (3,200ha; southeast of Paris), which receives over 3 million people annually. We sampled ticks over the entire forest area (from 220 forest stands with a total area of 35,200m(2)) and quantified the density of questing nymphs (DON), the prevalence of infection among nymphs (NIP), and the density of infected nymphs (DIN), which is the most important predictor of the human risk of Lyme borreliosis. For each of these response variables, we explored the relative roles of weather (saturation deficit), hosts (abundance indices of ungulates and Tamias sibiricus, an introduced rodent species), vegetation and forest cover, superficial soil composition, and the distance to forest roads. In total, 19,546 questing nymphs were collected and the presence of B. burgdorferi s. l. was tested in 3,903 nymphs by qPCR. The mean DON was 5.6 nymphs per 10m(2) (standard deviation=10.4) with an average NIP of 10.1% (standard deviation=0.11). The highest DIN was 8.9 infected nymphs per 10m(2), with a mean of 0.59 (standard deviation=0.6). Our mapping and modeling revealed a strong heterogeneity of risk within the forest. The highest risk was found in the eastern part of the forest and localized patches in the northwestern part. Lyme borreliosis risk was positively associated with stands of deciduous trees (mainly oaks) and roe deer abundance. Contrary to expectations, DIN actually increased with distance from the point of introduction of T. sibiricus (i.e., DIN was higher in areas with potentially lower abundances of T. sibiricus). Thus, despite the fact that T. sibiricus is an important reservoir host for B. burgdorferi s. l., our study found that other explanatory factors played a more important role in determining the density of infected ticks. Precise mapping of the risk of exposure to Lyme borreliosis in a highly visited forest represents an important tool for targeting prevention and control measures, as well as making the general public and local health officials aware of the risks.


Asunto(s)
Grupo Borrelia Burgdorferi/aislamiento & purificación , Ixodes/crecimiento & desarrollo , Ixodes/microbiología , Enfermedad de Lyme/epidemiología , Densidad de Población , Animales , Bosques , Humanos , Ninfa/crecimiento & desarrollo , Ninfa/microbiología , Paris/epidemiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Medición de Riesgo , Sciuridae/crecimiento & desarrollo
4.
J Crohns Colitis ; 9(11): 982-7, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26351388

RESUMEN

BACKGROUND AND AIM: Anti-tumour necrosis factor [TNF] agents have dramatically improved the prognosis of inflammatory bowel disease [IBD]. However, despite their good safety profile, use of these agents may lead to paradoxical manifestations involving skin or joints. Pathogenesis of such side effects is poorly understood and may involve anti-TNF pharmacokinetics. The aim of the present study was to look for an association between infliximab trough levels [ITL] and cutaneous [CPM] or rheumatological [RPM] paradoxical manifestations. METHODS: IBD patients receiving infliximab as maintenance therapy were included in a cross-sectional prospective monocentre study. At inclusion, patients had an ITL measurement [LISA-TRACKER®, Biomedical Diagnostics BMD] and were assessed for paradoxical manifestations: a CPM was defined by new onset or exacerbation of pre-existing psoriasis lesions during IFX therapy, and an RPM by new onset of severe poly-arthralgia during IFX therapy. RESULTS: Among the 121 patients included [69 female; median age: 38.9 years; 92 with Crohn's disease], 7% had CPM and 8% RPM. Median ITL values were 5.87 [range: 0.52-19.53] µg/ml in patients with CPM and 1.90 [0.00-13.5] µg/ml in those with RPM, as compared respectively with 5.12 [0.00-49.12] µg/ml in patients without CPM [p = 0.56] and 5.57 [0.00-49.12] µg/ml in those without RPM [p = 0.058]. No prognostic factor was associated with CPM. The single factor associated with RPM was elevated antinuclear antibodies. CONCLUSION: ITL were not elevated in IBD patients developing cutaneous or rheumatological paradoxical manifestations when receiving IFX as maintenance therapy. As suggested by the high level of antinuclear antibodies, RPM could be related to an induced autoimmune disorder.


Asunto(s)
Artritis Reumatoide/etiología , Fármacos Gastrointestinales/farmacocinética , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Infliximab/farmacocinética , Quimioterapia de Mantención/efectos adversos , Psoriasis/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artritis Reumatoide/diagnóstico , Estudios de Casos y Controles , Estudios Transversales , Femenino , Fármacos Gastrointestinales/sangre , Fármacos Gastrointestinales/uso terapéutico , Humanos , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/complicaciones , Infliximab/sangre , Infliximab/uso terapéutico , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Psoriasis/diagnóstico , Adulto Joven
5.
Mol Psychiatry ; 19(12): 1326-35, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24535457

RESUMEN

Amyloid beta (Aß) peptides are the major components of senile plaques, one of the main pathological hallmarks of Alzheimer disease (AD). However, Aß peptides' functions are not fully understood and seem to be highly pleiotropic. We hypothesized that plasma Aß peptides concentrations could be a suitable endophenotype for a genome-wide association study (GWAS) designed to (i) identify novel genetic factors involved in amyloid precursor protein metabolism and (ii) highlight relevant Aß-related physiological and pathophysiological processes. Hence, we performed a genome-wide association meta-analysis of four studies totaling 3 528 healthy individuals of European descent and for whom plasma Aß1-40 and Aß1-42 peptides levels had been quantified. Although we did not observe any genome-wide significant locus, we identified 18 suggestive loci (P<1 × 10(-)(5)). Enrichment-pathway analyses revealed canonical pathways mainly involved in neuronal functions, for example, axonal guidance signaling. We also assessed the biological impact of the gene most strongly associated with plasma Aß1-42 levels (cortexin 3, CTXN3) on APP metabolism in vitro and found that the gene protein was able to modulate Aß1-42 secretion. In conclusion, our study results suggest that plasma Aß peptides levels are valid endophenotypes in GWASs and can be used to characterize the metabolism and functions of APP and its metabolites.


Asunto(s)
Envejecimiento/sangre , Envejecimiento/genética , Péptidos beta-Amiloides/sangre , Fragmentos de Péptidos/sangre , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Estudio de Asociación del Genoma Completo , Células HEK293 , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Polimorfismo de Nucleótido Simple , Población Blanca/genética
6.
Mol Psychiatry ; 18(11): 1225-34, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23399914

RESUMEN

Genome-wide association studies (GWAS) have identified a region upstream the BIN1 gene as the most important genetic susceptibility locus in Alzheimer's disease (AD) after APOE. We report that BIN1 transcript levels were increased in AD brains and identified a novel 3 bp insertion allele ∼28 kb upstream of BIN1, which increased (i) transcriptional activity in vitro, (ii) BIN1 expression levels in human brain and (iii) AD risk in three independent case-control cohorts (Meta-analysed Odds ratio of 1.20 (1.14-1.26) (P=3.8 × 10(-11))). Interestingly, decreased expression of the Drosophila BIN1 ortholog Amph suppressed Tau-mediated neurotoxicity in three different assays. Accordingly, Tau and BIN1 colocalized and interacted in human neuroblastoma cells and in mouse brain. Finally, the 3 bp insertion was associated with Tau but not Amyloid loads in AD brains. We propose that BIN1 mediates AD risk by modulating Tau pathology.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Predisposición Genética a la Enfermedad/genética , Proteínas Nucleares/genética , Proteínas Supresoras de Tumor/genética , Proteínas tau/metabolismo , Proteínas Adaptadoras Transductoras de Señales/biosíntesis , Enfermedad de Alzheimer/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/patología , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Proteínas de Drosophila/deficiencia , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Endofenotipos , Expresión Génica/genética , Humanos , Ratones , Degeneración Nerviosa/genética , Degeneración Nerviosa/patología , Proteínas Nucleares/biosíntesis , Placa Amiloide/patología , Polimorfismo de Nucleótido Simple/genética , Sinaptosomas/patología , Factores de Transcripción/deficiencia , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/biosíntesis , Proteínas tau/antagonistas & inhibidores
7.
J Evol Biol ; 26(3): 612-24, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23331296

RESUMEN

Adaptation to new environments is a key feature in evolution promoting divergence in morphological structures under selection. The house mouse (Mus musculus domesticus) introduced on the Sub-Antarctic Guillou Island (Kerguelen Archipelago) had and still has to face environmental conditions that likely shaped the pattern and pace of its insular evolution. Since mouse arrival on the island, probably not more than two centuries ago, ecological conditions dramatically differed from those available to their Western European commensal source populations. In addition, over the last two decades, the plant and animal communities of Guillou Island were considerably modified by the eradication of rabbits, the effects of climate change and the spread of invasive species detrimental to native communities. Under such a changing habitat, the mouse response was investigated using a morphometric quantification of mandible and molar tooth, two morphological structures related to food processing. A marked differentiation of the insular mice compared with their relatives from Western Europe was documented for both mandibles and molar shapes. Moreover, these shapes changed through the 16 years of the record, in agreement with expectations of drift for the molar, but more than expected by chance for the mandible. These results suggest that mice responded to the recent changes in food resources, possibly with a part of plastic variation for the mandible prone to bone remodelling. This pattern exemplifies the intricate interplay of evolution, ecology and plasticity that is a probable key of the success of such an invasive rodent facing pronounced shifts in food resources exploitation under a changing environment.


Asunto(s)
Especies Introducidas , Mandíbula/anatomía & histología , Ratones/anatomía & histología , Diente Molar/anatomía & histología , Animales , Regiones Antárticas , Evolución Biológica , Ecosistema , Europa (Continente) , Islas , Análisis de Componente Principal , Caracteres Sexuales , Cráneo/anatomía & histología , Factores de Tiempo
8.
Eur Phys J E Soft Matter ; 35(6): 45, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22692685

RESUMEN

Granular pastes are dense dispersions of non-colloidal grains in a simple or a complex fluid. Typical examples are the coating, gluing or sealing mortars used in building applications. We study the rupture of a thick layer of mortar paste in a simple pulling test where the paste is confined between two flat surfaces. It is shown that, depending on the rheological properties of the paste and the plate separation velocity, two main failure modes are obtained. The first mode is the inwards shear flow of the paste with viscous fingering instabilities, similarly to what has been observed with Newtonian fluids and with non-Newtonian colloidal suspensions or polymer solutions. The second failure mode is stemming from the expansion of bubbles, similarly to what has been observed in soft adhesive polymer layers and, more recently, in highly viscous fluids. It is shown that the crossover between the two failure modes is determined by the conditions required to generate a pressure drop able to trigger the growth of pre-existing micro-bubbles smaller than the inter-granular distance.

9.
Int J Parasitol ; 42(8): 781-8, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22732161

RESUMEN

Wild birds are important hosts for vector-borne pathogens, especially those borne by ticks. However, few studies have been conducted on the role of different bird species within a community as hosts of vector-borne pathogens. This study addressed individual and species factors that could explain the burden of Ixodes ricinus on forest birds during the reproductive periods of both vectors and hosts. The goal was to identify which bird species contribute the most to the tick population at the community level. Birds were mist-netted on four plots in 2008 and on seven plots in 2009 in two forests (Sénart and Notre Dame, near Paris, France). The dependence of the tick load per bird upon environmental conditions (questing nymph density, year and plot) and on host species traits (species, age, sex, body size, vertical space use, level of innate and acquired immunity) was analysed. Finally, the relative contribution of each bird species to the local dynamics of ticks was estimated, while accounting for their respective abundance. Tick burden differed markedly between bird species and varied according to questing nymph density. Bird species with a high body mass, those that forage low in the vegetation, and those that had a high innate immune response and a high spleen mass were more likely to have a high tick burden. Four species (the Common Blackbird, Turdus merula, the European Robin, Erithacus rubecula, the Song Thrush, Turdus philomelos, and the Winter Wren, Troglodytes troglodytes) hosted more than 90% of the ticks in the local bird community. These species, and particularly T. merula which was host to a high proportion of the nymphs, are likely to contribute significantly to the circulation of pathogens for which they are competent, such as the agent of Lyme borreliosis.


Asunto(s)
Vectores Arácnidos/microbiología , Aves/parasitología , Borrelia burgdorferi/fisiología , Especificidad del Huésped , Ixodes/microbiología , Ixodes/fisiología , Enfermedad de Lyme/microbiología , Animales , Animales Salvajes/clasificación , Animales Salvajes/parasitología , Animales Salvajes/fisiología , Aves/clasificación , Aves/fisiología , Cruzamiento , Femenino , Francia , Humanos , Enfermedad de Lyme/transmisión , Masculino , Estaciones del Año
10.
Appl Environ Microbiol ; 77(16): 5716-21, 2011 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-21705536

RESUMEN

Little attention has been given in scientific literature to how introduced species may act as a new host for native infectious agents and modify the epidemiology of a disease. In this study, we investigated whether an introduced species, the Siberian chipmunk (Tamias sibiricus barberi), was a potentially new reservoir host for Borrelia burgdorferi sensu lato, the causative agent of Lyme disease. First, we ascertained whether chipmunks were infected by all of the B. burgdorferi sensu lato genospecies associated with rodents and available in their source of infection, questing nymphs. Second, we determined whether the prevalence and diversity of B. burgdorferi sensu lato in chipmunks were similar to those of a native reservoir rodent, the bank vole (Myodes glareolus). Our research took place between 2006 and 2008 in a suburban French forest, where we trapped 335 chipmunks and 671 voles and collected 743 nymphs of ticks that were questing for hosts by dragging on the vegetation. We assayed for B. burgdorferi sensu lato with ear biopsy specimens taken from the rodents and in nymphs using PCR and restriction fragment length polymorphism (RFLP). Chipmunks were infected by the three Borrelia genospecies that were present in questing nymphs and that infect rodents (B. burgdorferi sensu stricto, B. afzelii, and B. garinii). In contrast, voles hosted only B. afzelii. Furthermore, chipmunks were more infected (35%) than voles (16%). These results may be explained by the higher exposure of chipmunks, because they harbor more ticks, or by their higher tolerance of other B. burgdorferi sensu lato genospecies than of B. afzelii. If chipmunks are competent reservoir hosts for B. burgdorferi sensu lato, they may spill back B. burgdorferi sensu lato to native communities and eventually may increase the risk of Lyme disease transmission to humans.


Asunto(s)
Arvicolinae/microbiología , Grupo Borrelia Burgdorferi/genética , Variación Genética , Especies Introducidas , Sciuridae/microbiología , Animales , Arvicolinae/parasitología , Biopsia/veterinaria , Grupo Borrelia Burgdorferi/patogenicidad , Reservorios de Enfermedades , Francia , Genes de ARNr , Ixodes/microbiología , Enfermedad de Lyme/epidemiología , Enfermedad de Lyme/microbiología , Ninfa/microbiología , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Prevalencia , ARN Ribosómico 16S/genética , Sciuridae/genética , Sciuridae/parasitología
12.
Vet Parasitol ; 172(1-2): 172-6, 2010 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-20493636

RESUMEN

Introduced pets released in natura can lead to sanitary risks for native fauna and humans. We analysed the macroparasite fauna of a total of 49 Pallas's squirrels, Callosciurus erythraeus, from two populations introduced into urbanised areas in Europe (n=16 female symbol and 13 male symbol from Antibes, France, 43 degrees 33'N-7 degrees 7'E; n=11 female symbol and 9 male symbol in from Dadizele, Belgium, 50 degrees 52'N-3 degrees 5'E). Of the 185 identified ectoparasites from Antibes, 183 were sucking lice Enderleinellus kumadai, with male squirrels 10 times more intensely infested than females. The flea Nosopsyllus fasciatus was found on two hosts. No hard ticks were recovered. Of the 131 arthropods specimens from Dadizele, 45 belonged to E. kumadai, with male squirrels three times more intensely infested than females. Eighty-six arthropods belonged to another sucking louse, Hoplopleura erismata, with males infested twice as intensely as females. No fleas or hard ticks were found. We only found 12 immature Hymenolepis sp. cestodes in the small intestine of three squirrels from Antibes and two immature Mastophorus sp. female nematodes in the stomach of a squirrel from Dadizele. We found no other helminths in the body cavity, heart, lung, liver, kidney or bladder. The macroparasite fauna of these two squirrel populations is consistent with what is expected from an introduced host, i.e., a few species dominated by specialist taxa imported with founders. The scarcity of other rodent species in the urbanized areas where Pallas's squirrels were sampled may explain the low variety of newly acquired macroparasites. The discrepancy in sucking lice infestations between males and females could be due to differences in either behaviour or physiology in this non-sexually dimorphic host. Based on the macroparasites found in this study, we expect minimal sanitary risks for both native fauna and humans in urbanized habitats such as those in our study.


Asunto(s)
Artrópodos/crecimiento & desarrollo , Helmintos/crecimiento & desarrollo , Enfermedades de los Roedores/parasitología , Sciuridae , Animales , Bélgica , Femenino , Francia , Masculino , Factores Sexuales , Estadísticas no Paramétricas , Población Urbana
13.
Int J Parasitol ; 40(11): 1277-83, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20406644

RESUMEN

By serving as hosts for native vectors, introduced species can surpass native hosts in their role as major reservoirs of local pathogens. During a 4-year longitudinal study, we investigated factors that affected infestation by ixodid ticks on both introduced Siberian chipmunks Tamias sibiricus barberi and native bank voles Myodes glareolus in a suburban forest (Forêt de Sénart, Ile-de-France). Ticks were counted on adult bank voles and on adult and young chipmunks using regular monthly trapping sessions, and questing ticks were quantified by dragging. At the summer peak of questing Ixodes ricinus availability, the average tick load was 27-69 times greater on adult chipmunks than on adult voles, while average biomass per hectare of chipmunks and voles were similar. In adult chipmunks, individual effects significantly explained 31% and 24% of the total variance of tick larvae and nymph burdens, respectively. Male adult chipmunks harboured significantly more larvae and nymphs than adult females, and than juveniles born in spring and in summer. The higher tick loads, and more specifically the ratio of nymphs over larvae, observed in chipmunks may be caused by a higher predisposition--both in terms of susceptibility and exposure--to questing ticks. Tick burdens were also related to habitat and seasonal variation in age- and sex-related space use by both rodents. Introduced chipmunks may thus have an important role in the dynamics of local vector-borne pathogens compared with native reservoir hosts such as bank voles.


Asunto(s)
Arvicolinae/parasitología , Enfermedades de los Roedores/parasitología , Sciuridae/parasitología , Infestaciones por Garrapatas/veterinaria , Garrapatas/fisiología , Animales , Femenino , Francia , Masculino , Infestaciones por Garrapatas/parasitología , Árboles
14.
Mol Psychiatry ; 14(11): 1004-16, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19204726

RESUMEN

The only recognized genetic determinant of the common forms of Alzheimer's disease (AD) is the epsilon 4 allele of the apolipoprotein E gene (APOE). To identify new candidate genes, we recently performed transcriptomic analysis of 2741 genes in chromosomal regions of interest using brain tissue of AD cases and controls. From 82 differentially expressed genes, 1156 polymorphisms were genotyped in two independent discovery subsamples (n=945). Seventeen genes exhibited at least one polymorphism associated with AD risk, and following correction for multiple testing, we retained the interleukin (IL)-33 gene. We first confirmed that the IL-33 expression was decreased in the brain of AD cases compared with that of controls. Further genetic analysis led us to select three polymorphisms within this gene, which we analyzed in three independent case-control studies. These polymorphisms and a resulting protective haplotype were systematically associated with AD risk in non-APOE epsilon 4 carriers. Using a large prospective study, these associations were also detected when analyzing the prevalent and incident AD cases together or the incident AD cases alone. These polymorphisms were also associated with less cerebral amyloid angiopathy (CAA) in the brain of non-APOE epsilon 4 AD cases. Immunohistochemistry experiments finally indicated that the IL-33 expression was consistently restricted to vascular capillaries in the brain. Moreover, IL-33 overexpression in cellular models led to a specific decrease in secretion of the A beta(40) peptides, the main CAA component. In conclusion, our data suggest that genetic variants in IL-33 gene may be associated with a decrease in AD risk potentially in modulating CAA formation.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/genética , Interleucinas/genética , Interleucinas/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Animales , Apolipoproteína E4/genética , Encéfalo/metabolismo , Células COS , Estudios de Casos y Controles , Línea Celular Transformada , Angiopatía Amiloide Cerebral/genética , Angiopatía Amiloide Cerebral/metabolismo , Angiopatía Amiloide Cerebral/patología , Chlorocebus aethiops , Femenino , Estudios de Seguimiento , Carga Genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Interleucina-33 , Cooperación Internacional , Masculino , Neuroblastoma , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Fragmentos de Péptidos/metabolismo , Polimorfismo de Nucleótido Simple , Modelos de Riesgos Proporcionales , ARN Mensajero/metabolismo , Estudios Retrospectivos , Transfección/métodos
15.
Mol Psychiatry ; 14(1): 106-16, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17893704

RESUMEN

To more rapidly identify candidate genes located within chromosomal regions of interest defined by genome scan studies in Alzheimer's disease (AD), we have developed a customized microarray containing all the ORFs (n=2741) located within nine of these regions. Levels of gene expression were assessed in total RNA from brain tissue of 12 controls and 12 AD patients. Of all genes showing differential expression, we focused on the ornithine transcarbamylase (OTC) gene on Xp21.1., a key enzyme of the urea cycle which we found to be expressed in AD brains but not in controls, as confirmed by RT-PCR. We also detected mRNA expression of all the other urea cycle enzymes in AD brains. Immunochemistry experiments revealed that the OTC expression was strictly restricted to vascular endothelial cells in brain. Furthermore, OTC activity was 880% increased in the CSF of probable AD cases compared with controls. We analysed the association of the OTC -389 G/A and -241 A/G promoter polymorphisms with the risk of developing AD. We observed that rare haplotypes may be associated with the risk of AD through a possible modulation of the methylation of the OTC promoter. In conclusion, our results suggest the involvement of a new pathway in AD brains involving the urea cycle.


Asunto(s)
Enfermedad de Alzheimer/enzimología , Expresión Génica/fisiología , Ornitina Carbamoiltransferasa/metabolismo , Polimorfismo de Nucleótido Simple , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/fisiopatología , Encéfalo/metabolismo , Análisis Mutacional de ADN/métodos , Femenino , Genotipo , Humanos , Masculino , Análisis por Micromatrices/métodos , Ornitina Carbamoiltransferasa/genética , Factores Sexuales
16.
Parasite ; 15(2): 175-8, 2008 Jun.
Artículo en Francés | MEDLINE | ID: mdl-18642512

RESUMEN

A new sucking louse is recorded for the French Anopluran fauna, Enderleinellus tomiasis found on the introduced Sciurid Tamias sibiricus. This observation highlights the maintenance of parasites when introduced with their hosts and when their hosts settle into a novel environments. It suggests a common origin for two out of four populations of Siberian chipmunks examined. The authors describe the morphological criteria that allow the distinction between the two species of Enderleinellus and each infecting a sciurid host found in our country.


Asunto(s)
Anoplura/clasificación , Infestaciones por Piojos/veterinaria , Filogenia , Enfermedades de los Roedores/parasitología , Sciuridae/parasitología , Animales , Femenino , Francia , Infestaciones por Piojos/parasitología , Masculino , Especificidad de la Especie
17.
Parasite ; 15(1): 35-43, 2008 Mar.
Artículo en Francés | MEDLINE | ID: mdl-18416245

RESUMEN

We examined the fleas community in an introduced population of Siberian chipmunks, Tamias sibiricus, between 2005 and 2007, in the Forest of Sénart (Essonne, France). We collected and identified 383 fleas on 463 chipmunks (total: 1,891 captures on 471 chipmunks). In 2005, 120 fleas were also collected on 65 bank voles, Clethrionomys glareolus, and on 25 wood mice, Apodemus sylvaticus, trapped within the same area. Ceratophyllus sciurorum sciurorum formed 73.6% of the chipmunks' flea community, with an annual prevalence (P) ranging between 8 and 13% and a mean intensity (I) ranging between 1.1 and 1.6 fleas per individual. Among the six other species infecting this Sciurid, Ctenophthalmus agyrtes impavidus constituted 17.2% (P: 1.6-2.2%; I: 1.1-2.6), and Megabothris turbidus 8.1% (P: 0.8-1.9%; I: 1.0-1.4) of the flea community, respectively. These last two species represented respectively 60.8% and 36.6% of the flea community on the bank vole and the wood mouse. Originated from Asia, chipmunks did not import any flea species to Sénart, probably because they were used as pets before their release in the wild. Abundance in C. s. sciurorum increased with adult chipmunk density and with juvenile density in summer. On adult chipmunks C. s. sciurorum tented to decrease with increasing abundance of red squirrels (Sciurus vulgaris]. Moreover, the two other flea species mainly infected young chipmunks during the fall, and their number was not related to chipmunk density. However, the distribution of species within the flea community became more balanced with increase juvenile chipmunk density. Overall, these results indicate that the close phyletic relationship between chipmunks and red squirrels contributed in the acquisition and the spread of fleas by chipmunks. Primary and secondary hosts densities, their habitat use, and more specifically burrowing activities and tree canopy use, also played a role in the spread of fleas on chipmunks.


Asunto(s)
Infestaciones Ectoparasitarias/veterinaria , Enfermedades de los Roedores/epidemiología , Sciuridae/parasitología , Siphonaptera/clasificación , Siphonaptera/crecimiento & desarrollo , Factores de Edad , Animales , Arvicolinae/parasitología , Reservorios de Enfermedades/veterinaria , Infestaciones Ectoparasitarias/epidemiología , Infestaciones Ectoparasitarias/transmisión , Femenino , Francia , Masculino , Murinae/parasitología , Filogenia , Densidad de Población , Dinámica Poblacional , Prevalencia , Enfermedades de los Roedores/transmisión , Estaciones del Año , Especificidad de la Especie
18.
J Gen Virol ; 89(Pt 1): 341-347, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18089759

RESUMEN

It has been shown previously that ovine prion protein (PrP(C)) renders rabbit epithelial RK13 cells permissive to the multiplication of ovine prions, thus providing evidence that species barriers can be crossed in cultured cells through the expression of a relevant PrP(C). The present study significantly extended this observation by showing that mouse and bank vole prions can be propagated in RK13 cells that express the corresponding PrP(C). Importantly, the respective molecular patterns of abnormal PrP (PrP(res)) and, where examined, the neuropathological features of the infecting strains appeared to be maintained during the propagation in cell culture. These findings indicate that RK13 cells can be genetically engineered to replicate prion strains faithfully from different species. Such an approach may facilitate investigations of the molecular basis of strain identity and prion diversity.


Asunto(s)
Priones/patogenicidad , Animales , Arvicolinae , Línea Celular , Riñón/patología , Ratones , Priones/genética , Priones/aislamiento & purificación , Conejos
19.
Int J Oral Maxillofac Surg ; 35(7): 636-42, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16542822

RESUMEN

Recently developed computer applications provide tools for planning cranio-maxillofacial interventions based on 3-dimensional (3D) virtual models of the patient's skull obtained from computed-tomography (CT) scans. Precise knowledge of the location of the mid-facial plane is important for the assessment of deformities and for planning reconstructive procedures. In this work, a new method is presented to automatically compute the mid-facial plane on the basis of a surface model of the facial skeleton obtained from CT. The method matches homologous surface areas selected by the user on the left and right facial side using an iterative closest point optimization. The symmetry plane which best approximates this matching transformation is then computed. This new automatic method was evaluated in an experimental study. The study included experienced and inexperienced clinicians defining the symmetry plane by a selection of landmarks. This manual definition was systematically compared with the definition resulting from the new automatic method: Quality of the symmetry planes was evaluated by their ability to match homologous areas of the face. Results show that the new automatic method is reliable and leads to significantly higher accuracy than the manual method when performed by inexperienced clinicians. In addition, the method performs equally well in difficult trauma situations, where key landmarks are unreliable or absent.


Asunto(s)
Huesos Faciales/cirugía , Imagenología Tridimensional/métodos , Modelos Anatómicos , Cirugía Asistida por Computador/métodos , Algoritmos , Cefalometría , Gráficos por Computador , Huesos Faciales/diagnóstico por imagen , Humanos , Planificación de Atención al Paciente , Estadísticas no Paramétricas , Tomografía Computarizada por Rayos X
20.
J Helminthol ; 77(3): 247-53, 2003 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-12895284

RESUMEN

The reproductive activity of feral male mice on an island of the sub-Antarctic Kerguelen archipelago was influenced by biological factors depending on periods within the breeding season. After having controlled host reproductive activity indices for body size, i.e. age, and body condition effects, Syphacia obvelata prevalence did not vary with host reproductive status or age either during the beginning or the middle-end of the reproductive season. Considering the beginning of the breeding season, worm abundance was more pronounced in males the year following a strong winter crash of the population than in years when high over wintering survival occurred. During the middle-end of the breeding season, males with the highest reproductive status were more infected than males with a lower reproductive status in years when oldest individuals dominated the population. It is suggested that this situation was due to an endocrine related increased host susceptibility partly influenced by a change in the age structure of the population, and that an increase in worm transmission was not directly related to male activity concurrent with reproductive status, nor to population density.


Asunto(s)
Ratones/parasitología , Oxiuriasis/veterinaria , Oxyuroidea/aislamiento & purificación , Enfermedades de los Roedores/fisiopatología , Animales , Regiones Antárticas/epidemiología , Biometría , Constitución Corporal , Modelos Lineales , Masculino , Oxiuriasis/epidemiología , Oxiuriasis/fisiopatología , Prevalencia , Reproducción , Enfermedades de los Roedores/epidemiología , Estaciones del Año
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