Differential distribution of tau proteins in developing cat cerebellum.

The differential distribution and phosphorylation of tau proteins in cat cerebellum was studied with two well characterized antibodies, TAU-1 and TAU-2. TAU-1 detects tau proteins in axons, and the epitope in perikarya and dendrites is masked by phosphorylation. TAU-2 detects a phosphorylation-independent epitope on tau proteins. The molecular composition of tau proteins in the range of 45 kD to 64 kD at birth changed after the first postnatal month to a set of several adult variants of higher molecular weights in the range of 59 kD to 95 kD. The appearance of tau proteins in subsets of axons corresponds to the axonal maturation of cerebellar local-circuit neurons in granular and molecular layers and confirms previous studies. Tau proteins were also identified in synapses by immunofluorescent double-staining with synapsin I, located in the pinceau around the Purkinje cells, and in glomeruli. Dephosphorylation of juvenile cerebellar tissue by alkaline phosphatase indicated indirectly the presence of differentially phosphorylated tau forms mainly in juvenile ages. Additional TAU-1 immunoreactivity was unmasked in numerous perikarya and dendrites of stellate cells, and in cell bodies of granule cells. Purkinje cell bodies were stained transiently at juvenile ages. During postnatal development, the intensity of the phosphate-dependent staining decreased, suggesting that phosphorylation of tau proteins in perikarya and dendrites may be essential for early steps in neuronal morphogenesis during cat cerebellum development.

Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis.

OBJECTIVE: Familial cold urticaria (FCU) and Muckle-Wells syndrome (MWS) are dominantly inherited autoinflammatory disorders that cause rashes, fever, arthralgia, and in some subjects, AA amyloidosis, and have been mapped to chromosome 1q44. Sensorineural deafness in MWS, and provocation of symptoms by cold in FCU, are distinctive features. This study was undertaken to characterize the genetic basis of FCU, MWS, and an overlapping disorder in French Canadian, British, and Indian families, respectively. METHODS: Mutations in the candidate gene NALP3, which has also been named CIAS1 and PYPAF1, were sought in the study families, in a British/Spanish patient with apparent sporadic MWS, and in matched population controls. Identified variants were sought in 50 European subjects with uncharacterized, apparently sporadic periodic fever syndromes, 48 subjects with rheumatoid arthritis (RA), and 19 subjects with juvenile idiopathic arthritis (JIA). RESULTS: Point mutations, encoding putative protein variants R262W and L307P, were present in all affected members of the Indian and French Canadian families, respectively, but not in controls. The R262W variant was also present in the subject with sporadic MWS. The V200M variant was present in all affected members of the British family with MWS, in 2 of the 50 subjects with uncharacterized periodic fevers, and in 1 of 130 Caucasian and 2 of 48 Indian healthy controls. No mutations were identified among the subjects with RA or JIA. CONCLUSION: These findings confirm that mutations in the NALP3/CIAS1/PYPAF1 gene are associated with FCU and MWS, and that disease severity and clinical features may differ substantially within and between families. Analysis of this gene will improve classification of patients with inherited or apparently sporadic periodic fever syndromes.

Spondylarthropathies in children--are they different from those in adults?

Juvenile spondylarthropathies (JSpAs) comprise a group of rheumatic diseases distinct from other categories of juvenile arthritis. Several classification systems have been applied, and some are specific for children, such as the seronegative enthesopathy and arthropathy (SEA) syndrome and the enthesitis-related arthritis, diagnostic forms in the International League of Associations for Rheumatism (ILAR) classification. JSpA seems more frequent than was previously believed, but actual epidemiological data show important variations between studies. Compared to adult patients, children with JSpA present with peripheral arthritis and enthesitis early in disease but sacroiliac and spine joints involvement many years later. A multidisciplinary team in a paediatric environment should be responsible for the management of children with spondylarthropathies to ensure the best care for these children with their chronic disease and risk of long-term disability. Recent advances in the treatment of rheumatic diseases with biological agents show promising results in children with JSpA. Further research needs to be conducted to increase our knowledge of the long-term outcome of these patients, to improve management, and to prevent long-term consequences of the disease.

Intra- and interindividual variation in flank gland secretions of free-ranging shrews Crocidura russula

Individual differences in Rank gland secretions were examined among males of the monogamous shrew Crocidura russula during the breeding and nonbreeding seasons. Gas chromatography was used to measure intra- and interindividual variation of flank gland secretions of free-ranging shrews from different populations. The number of compounds detected by gas chromatographic analyses was correlated with body mass, flank gland size, and the presence of blood parasites in individual shrews. Very few compounds were detected from the Bank gland area of juvenile males. After they reached sexual maturity, however, the number of compounds detected from the Rank gland secretions increased significantly. At the beginning of the reproductive season 48 different compounds were detected from male flank gland secretions. In the middle of the breeding season 70 compounds were detected, while only 11 compounds were detected during the nonbreeding season. Few compounds were common to all males. There were more volatile compounds in the Bank gland secretions of males in the beginning of the breeding season than later in the breeding season. Males from the same population had fewer differences in the elution profile of compounds than males from different populations indicating that individuals from a distinct population have similar elution profiles of compounds and that each population has its own type of elution profile. No correlations were found between the number of compounds detected by gas chromatography for each male and the male's body mass or flank gland size. Blood parasites (trypanosomes, Trypanosoma crocidurae) were found in only three of 30 males investigated.

Change in individual growth rate and its link to gill-net fishing in two sympatric whitefish species

Size-selective fishing is expected to affect traits such as individual growth rate, but the relationship between the fishery-linked selection differentials and the corresponding phenotypic changes is not well understood. We analysed a 25-year monitoring survey of sympatric populations of the two Alpine whitefish Coregonus albellus and C. fatioi. We determined the fishing-induced selection differentials on growth rates, the actual change of growth rates over time, and potential indicators of reproductive strategies that may change over time. We found marked declines in adult growth rate and significant selection differentials that may partly explain the observed declines. However, when comparing the two sympatric species, the selection differentials on adult growth were stronger in C. albellus while the decline in adult growth rate seemed more pronounced in C. fatioi. Moreover, the selection differential on juvenile growth was significant in C. albellus but not in C. fatioi, while a significant reduction in juvenile growth over the last 25 years was only found in C. fatioi. Our results suggest that size-selective fishing affects the genetics for individual growth in these whitefish, and that the link between selection differentials and phenotypic changes is influenced by species-specific factors.

VEGF is required for growth and survival in neonatal mice.

We employed two independent approaches to inactivate the angiogenic protein VEGF in newborn mice: inducible, Cre-loxP- mediated gene targeting, or administration of mFlt(1-3)-IgG, a soluble VEGF receptor chimeric protein. Partial inhibition of VEGF achieved by inducible gene targeting resulted in increased mortality, stunted body growth and impaired organ development, most notably of the liver. Administration of mFlt(1-3)-IgG, which achieves a higher degree of VEGF inhibition, resulted in nearly complete growth arrest and lethality. Ultrastructural analysis documented alterations in endothelial and other cell types. Histological and biochemical changes consistent with liver and renal failure were observed. Endothelial cells isolated from the liver of mFlt(1-3)-IgG-treated neonates demonstrated an increased apoptotic index, indicating that VEGF is required not only for proliferation but also for survival of endothelial cells. However, such treatment resulted in less significant alterations as the animal matured, and the dependence on VEGF was eventually lost some time after the fourth postnatal week. Administration of mFlt(1-3)-IgG to juvenile mice failed to induce apoptosis in liver endothelial cells. Thus, VEGF is essential for growth and survival in early postnatal life. However, in the fully developed animal, VEGF is likely to be involved primarily in active angiogenesis processes such as corpus luteum development.

Reduced physical activity level and cardiorespiratory fitness in children with chronic diseases.

We aimed to compare physical activity level and cardiorespiratory fitness in children with different chronic diseases, such as type 1 diabetes mellitus (T1DM), obesity (OB) and juvenile idiopathic arthritis (JIA), with healthy controls (HC). We performed a cross-sectional study including 209 children: OB: n = 45, T1DM: n = 48, JIA: n = 31, and HC: n = 85. Physical activity level was assessed by accelerometer and cardiorespiratory fitness by a treadmill test. ANOVA, linear regressions and Pearson correlations were used. Children with chronic diseases had reduced total daily physical activity counts (T1DM 497 +/- 54 cpm, p = 0.003; JIA 518 +/- 28, p < 0.001, OB 590 +/- 25, p = 0.003) and cardiorespiratory fitness (JIA 39.3 +/- 1.7, p = 0.001, OB 41.7 +/- 1.2, p = 0.020) compared to HC (668 +/- 35 cpm; 45.3 +/- 0.9 ml kg(-1) min(-1), respectively). Only 60.4% of HC, 51.6% of OB, 38.1% of JIA and 38.5% of T1DM children met the recommended daily 60 min of moderate-to-vigorous physical activity. Low cardiorespiratory fitness was associated with female gender and low daily PA. Children with chronic diseases had reduced physical activity and cardiorespiratory fitness. As the benefits of PA on health have been well demonstrated during growth, it should be encouraged in those children to prevent a reduction of cardiorespiratory fitness and the development of comorbidities.

Enriched basaltic andesites from mid-crustal fractional crystallization, recharge, and assimilation (Pilavo Volcano, Western Cordillera of Ecuador)

The origin of andesite is an important issue in petrology because andesite is the main eruptive product at convergent margins, corresponds to the average crustal composition and is often associated with major Cu-Au mineralization. In this study we present petrographic, mineralogical, geochemical and isotopic data for basaltic andesites of the latest Pleistocene Pilavo volcano, one of the most frontal volcanoes of the Ecuadorian Quaternary arc, situated upon thick (30-50 km) mafic crust composed of accreted Cretaceous oceanic plateau rocks and overlying mafic to intermediate Late Cretaceous-Late Tertiary magmatic arcs. The Pilavo rocks are basaltic andesites (54-57 center dot 5 wt % SiO(2)) with a tholeiitic affinity as opposed to the typical calc-alkaline high-silica andesites and dacites (SiO(2) 59-66 wt %) of other frontal arc volcanoes of Ecuador (e.g. Pichincha, Pululahua). They have much higher incompatible element contents (e.g. Sr 650-1350 ppm, Ba 650-1800 ppm, Zr 100-225 ppm, Th 5-25 ppm, La 15-65 ppm) and Th/La ratios (0 center dot 28-0 center dot 36) than Pichincha and Pululahua, and more primitive Sr ((87)Sr/(86)Sr similar to 0 center dot 7038-0 center dot 7039) and Nd (epsilon(Nd) similar to +5 center dot 5 to +6 center dot 1) isotopic signatures. Pilavo andesites have geochemical affinities with modern and recent high-MgO andesites (e.g. low-silica adakites, Setouchi sanukites) and, especially, with Archean sanukitoids, for both of which incompatible element enrichments are believed to result from interactions of slab melts with peridotitic mantle. Petrographic, mineral chemistry, bulk-rock geochemical and isotopic data indicate that the Pilavo magmatic rocks have evolved through three main stages: (1) generation of a basaltic magma in the mantle wedge region by flux melting induced by slab-derived fluids (aqueous, supercritical or melts); (2) high-pressure differentiation of the basaltic melt (at the mantle-crust boundary or at lower crustal levels) through sustained fractionation of olivine and clinopyroxene, leading to hydrous, high-alumina basaltic andesite melts with a tholeiitic affinity, enriched in incompatible elements and strongly impoverished in Ni and Cr; (3) establishment of one or more mid-crustal magma storage reservoirs in which the magmas evolved through dominant amphibole and clinopyroxene (but no plagioclase) fractionation accompanied by assimilation of the modified plutonic roots of the arc and recharge by incoming batches of more primitive magma from depth. The latter process has resulted in strongly increasing incompatible element concentrations in the Pilavo basaltic andesites, coupled with slightly increasing crustal isotopic signatures and a shift towards a more calc-alkaline affinity. Our data show that, although ultimately originating from the slab, incompatible element abundances in arc andesites with primitive isotopic signatures can be significantly enhanced by intra-crustal processes within a thick juvenile mafic crust, thus providing an additional process for the generation of enriched andesites.

Quantifying network properties in multi-electrode recordings: spatiotemporal characterization and inter-trial variation of evoked gamma oscillations in mouse somatosensory cortex in vitro.

Linking the structural connectivity of brain circuits to their cooperative dynamics and emergent functions is a central aim of neuroscience research. Graph theory has recently been applied to study the structure-function relationship of networks, where dynamical similarity of different nodes has been turned into a "static" functional connection. However, the capability of the brain to adapt, learn and process external stimuli requires a constant dynamical functional rewiring between circuitries and cell assemblies. Hence, we must capture the changes of network functional connectivity over time. Multi-electrode array data present a unique challenge within this framework. We study the dynamics of gamma oscillations in acute slices of the somatosensory cortex from juvenile mice recorded by planar multi-electrode arrays. Bursts of gamma oscillatory activity lasting a few hundred milliseconds could be initiated only by brief trains of electrical stimulations applied at the deepest cortical layers and simultaneously delivered at multiple locations. Local field potentials were used to study the spatio-temporal properties and the instantaneous synchronization profile of the gamma oscillatory activity, combined with current source density (CSD) analysis. Pair-wise differences in the oscillation phase were used to determine the presence of instantaneous synchronization between the different sites of the circuitry during the oscillatory period. Despite variation in the duration of the oscillatory response over successive trials, they showed a constant average power, suggesting that the rate of expenditure of energy during the gamma bursts is consistent across repeated stimulations. Within each gamma burst, the functional connectivity map reflected the columnar organization of the neocortex. Over successive trials, an apparently random rearrangement of the functional connectivity was observed, with a more stable columnar than horizontal organization. This work reveals new features of evoked gamma oscillations in developing cortex.

Mucormycose rhino-orbito-cérébral: présentations cliniques [Rhino-orbito-cerebral mucormycosis: clinical presentation]

BACKGROUND: Rhino-orbito-cerebral mucormycosis is an opportunistic rapidly progressive infection affecting almost exclusively diabetic or immunocompromised patients. CASE REPORTS: Three cases are reported. For one patient mucormycosis was the first manifestation of juvenile diabetes and the evolution was favorable. In the second case the infection affected a known diabetic patient and the clinical course was fatal. The third patient was immunocompromised, showed mild clinical features and a rapidly fatal evolution, the diagnosis being made only postmortem. CONCLUSION: These three cases illustrate the wide clinical spectrum of rhino-orbito-cerebral mucormycosis, its serious nature and difficult diagnosis.

First evaluation of human sperm quality in various geographic regions of Switzerland

A decline in human sperm quality and quantity has been reported in numerous Western countries. This observation was also accompanied by an increase in urogenital malformations. The need for epidemiological studies dealing with unbiased populations in order to understand the causes of these observations is obvious. In Switzerland, the large majority of young men are asked to attend a military camp to be drafted into the army. A few weeks before this camp, conscripts were contacted and invited to participate in a large national study on semen quality. The participation was totally voluntary and anonymous. From September 2005 to June 2007, 770 volunteers filled out a questionnaire, underwent a clinical examination and provided sperm, blood and urine samples. Using self-rated health assessments, the observed cohort could be considered as healthy and no testicular cancer was found. Moreover, the testicular volumes, measured using Prader's orchidometry and ultrasonography, were comparable to those already published for young male populations. The median sperm concentration was 47 x 10(6)/ml, which is close to the concentration reported in Denmark, known to have the highest incidence of testicular cancer in Europe. Statistically significant differences were observed between regions with a lower sperm concentration for men residing in the Alps (43 x 10(6)/ml) and in the Zurich area (36 x 10(6)/ml) compared to men from West Plateau (54 x 10(6)/ml) and from the Jura (54 x 10(6)/ml). Such a regional discrepancy could be related to environmental factors, including endocrine disruptors. In order to confirm such regional differences more volunteers from the already studied regions should be studied and other parts of the country should be investigated. The rather low sperm concentration of Swiss young volunteers should be considered as a national health issue and investigated further.

Fièvre à répétition chez l'enfant: penser au syndrome de PFAPA [Periodic fever in children: keep in mind the PFAPA syndrome]

Les maladies autoinflammatoires font partie du diagnostic différentiel de l'état fébrile à répétition chez l’enfant. Ces maladies sont caractérisées par des poussées inflammatoires sans cause évidente. Certaines de ces maladies, comme la Fièvre méditerranéenne familiale, ont une origine génétique et nécessitent un traitement régulier pour éviter des conséquences graves à long terme. Le syndrome de PFAPA est la plus fréquente des fièvres récurrentes et son diagnostic se base sur des critères diagnostiques peu précis. Son traitement reste controversé. La prednisone en dose unique permet d'interrompre la poussée et l'amygdalectomie peut induire une rémission dans une majorité des cas. The autoinflammatory diseases should be considered in the differential diagnosis of recurrent fever in childhood. These diseases are characterized by inflammatory episodes without an evident cause. Some of these diseases, like the Familial Mediterranean Fever, have a genetic origin and need a chronic treatment to avoid severe complications on the long term. PFAPA syndrome is the most frequent cause of recurrent fever and is diagnosed based on unspecific criteria. The treatment is still controversial. One dose of Prednisone is able to interrupt the flare and tonsillectomy may induce a remission in the majority of the cases

Tests for sex-biased dispersal using bi-parentally inherited genetic markers.

Understanding why dispersal is sex-biased in many taxa is still a major concern in evolutionary ecology. Dispersal tends to be male-biased in mammals and female-biased in birds, but counter-examples exist and little is known about sex bias in other taxa. Obtaining accurate measures of dispersal in the field remains a problem. Here we describe and compare several methods for detecting sex-biased dispersal using bi-parentally inherited, codominant genetic markers. If gene flow is restricted among populations, then the genotype of an individual tells something about its origin. Provided that dispersal occurs at the juvenile stage and that sampling is carried out on adults, genotypes sampled from the dispersing sex should on average be less likely (compared to genotypes from the philopatric sex) in the population in which they were sampled. The dispersing sex should be less genetically structured and should present a larger heterozygote deficit. In this study we use computer simulations and a permutation test on four statistics to investigate the conditions under which sex-biased dispersal can be detected. Two tests emerge as fairly powerful. We present results concerning the optimal sampling strategy (varying number of samples, individuals, loci per individual and level of polymorphism) under different amounts of dispersal for each sex. These tests for biases in dispersal are also appropriate for any attribute (e.g. size, colour, status) suspected to influence the probability of dispersal. A windows program carrying out these tests can be freely downloaded from http://www.unil.ch/izea/softwares/fstat.html

Sleep deprivation induces transcriptional modifications of genes related to astrocyte-neuron lactate shuttle in astrocytes

Astrocytes play a key role in the neurometabolic coupling through the glycogen metabolism and the ''Astrocyte-Neuron Lactate Shuttle'' (ANLS). We previously reported that brain glycogen metabolism was affected by sleep deprivation (SD). Therefore, it is of prime interest to determine if a similar sleep loss also affects the ANLS functioning in astrocytes. To address this issue, we sleep deprived transgenic mice expressing the GFP under the control of the GFAP promoter and in which astrocytes can be isolated by FACS. The levels of expression of genes related to ANLS were assessed by qRT-PCR in the GFP-positive cells (GFPþ). The FVB/NTg( GFAP-GFP)Mes14/j mice were weaned at P20-P21 and underwent an instrumental 6 h SD at P23-P27. The SD was realized using the ''CaResS'' device which has been designed to minimize stress during SD. Control group corresponds to undisturbed mice. At the end of SD, mice were sacrificed and their cerebral cortex was rapidly dissected, cut in small pieces and enzymatically digested. After cell dissociation, GFPþ and GFP- cells were sorted by FACS and treated for RNA extraction. A quantitative RTPCR was realized using specific probes against different genes involved in ANLS. Results indicate that genes encoding the LDHb, the GLT1, the alpha2 subunit of the Na/KATPase pump as well as the GLUT1, were significantly increased in the GFPþ cells from SD mice. No significant change was observed in the GFP- cells from the same group. These results indicate that this approach is suitable to determine the transcriptional signature of SD in glial cells from juvenile animals. They also indicate that sleep loss induces transcriptional changes of genes involved in ANLS specifically in astrocytes. This could suggest that an adaptation of the ANLS at the transcriptional levels exists in pathophysiological conditions where neuronal activity is enhanced.