Beta-catenin Status in P?aediatric Medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics.

Medulloblastoma is the most frequent malignant paediatric brain tumour. The activation of the Wnt/beta-catenin pathway occurs in 10-15% of medulloblastomas and has been recently described as a marker for favourable patient outcome. We report a series of 72 paediatric medulloblastomas evaluated for beta-catenin protein expression, CTNNB1 mutations, and comparative genomic hybridization. Gene expression profiles were also available in a subset of 40 cases. Immunostaining of beta-catenin showed extensive nuclear staining (>50% of the tumour cells) in six cases and focal nuclear staining (<10% of cells) in three cases. The other cases either exhibited a signal strictly limited to the cytoplasm (58 cases) or were negative (five cases). CTNNB1 mutations were detected in all beta-catenin extensively nucleopositive cases. The expression profiles of these cases documented strong activation of the Wnt/beta-catenin pathway. Remarkably, five out of these six tumours showed a complete loss of chromosome 6. In contrast, cases with focal nuclear beta-catenin staining, as well as tumours with negative or cytoplasmic staining, never demonstrated CTNNB1 mutation, Wnt/beta-catenin pathway activation or chromosome 6 loss. Patients with extensive nuclear staining were significantly older at diagnosis and were in continuous complete remission after a mean follow-up of 75.7 months (range 27.5-121.2 months) from diagnosis. All three patients with focal nuclear staining of beta-catenin died within 36 months from diagnosis. Altogether, these data confirm and extend previous observations that CTNNB1-mutated tumours represent a distinct molecular subgroup of medulloblastomas with favourable outcome, indicating that therapy de-escalation should be considered. International consensus on the definition criteria of this distinct medulloblastoma subgroup should be achieved.

Post-switching beta synchronization reveals concomitant sensory reafferences and active inhibition processes

It is known that post-movement beta synchronization (PMBS) is involved both in active inhibition and in sensory reafferences processes. The aim of this study was examine the temporal and spatial dynamics of the PMBS involved during multi-limb coordination task. We investigated post-switching beta synchronization (assigned PMBS) using time-frequency and source estimations analyzes. Participants (n = 17) initiated an auditory-paced bimanual tapping. After a 1500 ms preparatory period, an imperative stimulus required to either selectively stop the left while maintaining the right unimanual tapping (Switch condition: SWIT) or to continue the bimanual tapping (Continue condition: CONT). PMBS significantly increased in SWIT compared to CONT with maximal difference within right central region in broad-band 14âeuro"30 Hz and within left central region in restricted-band 22âeuro"26 Hz. Source estimations localized these effects within right pre-frontal cortex and left parietal cortex, respectively. A negative correlation showed that participants with a low percentage of errors in SWIT had a large PMBS amplitude within right parietal and frontal cortices. This study shows for the first time simultaneous PMBS with distinct functions in different brain regions and frequency ranges. The left parietal PMBS restricted to 22âeuro"26 Hz could reflect the sensory reafferences of the right hand tapping disrupted by the switching. In contrast, the right pre-frontal PMBS in a broad-band 14âeuro"30 Hz is likely reflecting the active inhibition of the left hand stopped. Finally, correlations between behavioral performance and the magnitude of the PMBS suggest that beta oscillations can be viewed as a marker of successful active inhibition.

Automated Lesion Detection-Based Symptome Mapping In Patients With Sensory Deficits

The human brain is the most complex structure known. With its high number of cells, number of connections and number of pathways it is the source of every thought in the world. It consumes 25% of our oxygen and suffers very fast from a disruption of its supply. An acute event, like a stroke, results in rapid dysfunction referable to the affected area. A few minutes without oxygen and neuronal cells die and subsequently degenerate. Changes in the brains incoming blood flow alternate the anatomy and physiology of the brain. All stroke events leave behind a brain tissue lesion. To rapidly react and improve the prediction of outcome in stroke patients, accurate lesion detection and reliable lesion-based function correlation would be very helpful. With a number of neuroimaging and clinical data of cerebral injured patients this study aims to investigate correlations of structural lesion locations with sensory functions.

Chemical similarity among domesticated and wild genotypes of peanut based on n-alkanes profiles

The objective of this work was to analyze the epicuticular n-alkane profile of domesticated and wild peanut genotypes. Foliar epicuticular n-alkanes of four Arachis hypogaea genotypes and two wild species - A. monticola and A. stenosperma - were analyzed by gas chromatography. Chemical relationships between them were evaluated using the Dice coefficient and UPGMA method. Two clusters were formed: one with four A. hypogaea genotypes and the other with the two wild species. There is more similarity between the BR1 and LIGO-PE06 genotypes and between the BRS 151 L-7 and BRS Havana genotypes.

Genome-wide RNA polymerase II profiles and RNA accumulation reveal kinetics of transcription and associated epigenetic changes during diurnal cycles.

Interactions of cell-autonomous circadian oscillators with diurnal cycles govern the temporal compartmentalization of cell physiology in mammals. To understand the transcriptional and epigenetic basis of diurnal rhythms in mouse liver genome-wide, we generated temporal DNA occupancy profiles by RNA polymerase II (Pol II) as well as profiles of the histone modifications H3K4me3 and H3K36me3. We used these data to quantify the relationships of phases and amplitudes between different marks. We found that rhythmic Pol II recruitment at promoters rather than rhythmic transition from paused to productive elongation underlies diurnal gene transcription, a conclusion further supported by modeling. Moreover, Pol II occupancy preceded mRNA accumulation by 3 hours, consistent with mRNA half-lives. Both methylation marks showed that the epigenetic landscape is highly dynamic and globally remodeled during the 24-hour cycle. While promoters of transcribed genes had tri-methylated H3K4 even at their trough activity times, tri-methylation levels reached their peak, on average, 1 hour after Pol II. Meanwhile, rhythms in tri-methylation of H3K36 lagged transcription by 3 hours. Finally, modeling profiles of Pol II occupancy and mRNA accumulation identified three classes of genes: one showing rhythmicity both in transcriptional and mRNA accumulation, a second class with rhythmic transcription but flat mRNA levels, and a third with constant transcription but rhythmic mRNAs. The latter class emphasizes widespread temporally gated posttranscriptional regulation in the mouse liver.

Venom alkaloid and cuticular hydrocarbon profiles are associated with social organization, queen fertility status, and queen genotype in the fire ant Solenopsis invicta.

Queens in social insect colonies advertise their presence in the colony to: a) attract workers' attention and care; b) gain acceptance by workers as replacement or supplemental reproductives; c) prevent reproductive development in nestmates. We analyzed the chemical content of whole body surface extracts of adult queens of different developmental and reproductive stages, and of adult workers from monogyne (single colony queen) and polygyne (multiple colony queens) forms of the fire ant Solenopsis invicta. We found that the composition of the most abundant components, venom alkaloids, differed between queens and workers, as well as between reproductive and non-reproductive queens. Additionally, workers of the two forms could be distinguished by alkaloid composition. Finally, sexually mature, non-reproductive queens from polygyne colonies differed in their proportions of cis-piperidine alkaloids, depending on their Gp-9 genotype, although the difference disappeared once they became functional reproductives. Among the unsaturated cuticular hydrocarbons characteristic of queens, there were differences in amounts of alkenes/alkadienes between non-reproductive polygyne queens of different Gp-9 genotypes, between non-reproductive and reproductive queens, and between polygyne and monogyne reproductive queens, with the amounts increasing at a relatively higher rate through reproductive ontogeny in queens bearing the Gp-9 b allele. Given that the genotype-specific piperidine differences reflect differences in rates of reproductive maturation between queens, we speculate that these abundant and unique compounds have been co-opted to serve in fertility signaling, while the cuticular hydrocarbons now play a complementary role in regulation of social organization by signaling queen Gp-9 genotype.

Flour production from shrimp by-products and sensory evaluation of flour-based products

The objective of this work was to evaluate the production of flour using by-products (cephalothorax) obtained from the shrimp (Litopenaeus vannamei) industry, and to perform a sensory analysis of shrimp flour-based products. Physicochemical and microbiological analyses on fresh cephalothorax and on manufactured flour were performed, as well as the determination of cholesterol content of this flour, and the sensorial evaluation of soup and pastry made with this flour. By the microbiological analyses, no pathogenic microorganism was detected in the samples. Physicochemical analyses of flour showed high levels of protein (50.05%) and minerals (20.97%). Shrimp cephalothorax flour showed high levels of cholesterol. The sensory evaluation indicated a good acceptance of the products, with satisfactory acceptability index (81% for soup, and 83% for pastry), which indicates that shrimp cephalothorax in the form of flour has a potential for developing new products.

Shelf life and sensory assessment of tilapia quenelle during frozen storage

The objective of this work was to evaluate the shelf life and sensory attributes of tilapia quenelle. Treatments consisted of two types of packages - polyethylene zipper (retort pouch) (QA) and polyethylene waxed paper box (QB) - stored at -18ºC for 120 days. Tilapia quenelle was stable for all parameters established by Brazilian legislation. Average values of the evaluated attributes in different packages, during storage, showed no significant difference, except for the "refrigeration" flavor. However, during the storage period, there were significant differences for sensory attributes, as "moist appearance", fish and product aroma, and off flavors of "mud" and "refrigeration". Preserving product quality as for its sensory attributes, during storage, shows that tilapia quenelle is a convenience product and contributes to the increase of fish consumption.

P-wave velocities of samples from the Penninic of the western Alps along NFP20-west seismic-reflection profiles

Using the transit pulse method, we have determined compressional wave velocities of rocks from various geological units belonging to the Penninic zone along the NFP20-West profiles of the Swiss western Alps. The velocities have been measured at confining pressures up to 400 MPa, along three orthogonal axes defined by the macrostructure of the rocks. The samples analysed show a degree of metamorphism ranging from greenschist to eclogite facies. This collection includes schists, dolomites, gneisses and ophiolitic rocks. The mean velocities range from 5.9 km/s for a quartzitic calcschist to 7.9 km/s for an eclogitic metagabbro. The velocity anisotropy is as high as 20 %. The range of acoustic impedance is wide, from 15 to 27 10(6) kg/m2s. From these measurements, normal incident reflection coefficients for likely rock assemblages within and between geological units were estimated in order to interpret zone of the strong reflections recorded along the seismic profiles. Reflection coefficients as high as 0.17 could be determined.

Statistical variation of weld profiles and their expected influence on fatigue strength

The general objective of this study was to conduct astatistical analysis on the variation of the weld profiles and their influence on the fatigue strength of the joint. Weld quality with respect to its fatigue strength is of importance which is the main concept behind this thesis. The intention of this study was to establish the influence of weld geometric parameters on the weld quality and fatigue strength. The effect of local geometrical variations of non-load carrying cruciform fillet welded joint under tensile loading wasstudied in this thesis work. Linear Elastic Fracture Mechanics was used to calculate fatigue strength of the cruciform fillet welded joints in as-welded condition and under cyclic tensile loading, for a range of weld geometries. With extreme value statistical analysis and LEFM, an attempt was made to relate the variation of the cruciform weld profiles such as weld angle and weld toe radius to respective FAT classes.

Comparison of fatty acid profiles of edible meat, adipose tissues and muscles between cocks and capons

The effect of caponisation on fat composition by parts (wing, breast, thigh, and drumstick) and tissues (skin, subcutaneous adipose tissue, intermuscular adipose tissue and muscle) was examined in the present study and fatty acid profiles of abdominal fat and edible meat by parts and tissue components were determined. The sample was made up of twenty-eight castrated and twenty male Penedesenca Negra chicks reared under free-range conditions and slaughtered at 28 wk of age; the birds were castrated at four or eight weeks. Caponisation significantly increased (P < 0.01) the chemical fat content in all parts (16.31% to 37.98% in breast; 21.98% to 34.13% in wing; 21.09% to 49.57% in thigh; 14.33% to 24.82% in drumstick) and led to minor modifications in fat haracteristics, particularly in the thigh and the drumstick, where the unsaturated vs. saturated fatty acid ratio increased from 1.31 to 1.76 ( P < 0.01) and from 1.48 to 2.07 (P < 0.01), respectively. Delaying the age of castration from 4 to 8 weeks increased this ratio by 0.35 in the edible meat. Even though the profile of the abdominal fat is less saturated in capons, all changes occurring on fat quality after caponisation indicate that increased fatness after castration does not imply worse fat nutritional properties.

Muscle transcriptomic profiles in pigs with divergent phenotypes for fatness traits

BACKGROUND: Selection for increasing intramuscular fat content would definitively improve the palatability and juiciness of pig meat as well as the sensorial and organoleptic properties of cured products. However, evidences obtained in human and model organisms suggest that high levels of intramuscular fat might alter muscle lipid and carbohydrate metabolism. We have analysed this issue by determining the transcriptomic profiles of Duroc pigs with divergent phenotypes for 13 fatness traits. The strong aptitude of Duroc pigs to have high levels of intramuscular fat makes them a valuable model to analyse the mechanisms that regulate muscle lipid metabolism, an issue with evident implications in the elucidation of the genetic basis of human metabolic diseases such as obesity and insulin resistance. RESULTS: Muscle gene expression profiles of 68 Duroc pigs belonging to two groups (HIGH and LOW) with extreme phenotypes for lipid deposition and composition traits have been analysed. Microarray and quantitative PCR analysis showed that genes related to fatty acid uptake, lipogenesis and triacylglycerol synthesis were upregulated in the muscle tissue of HIGH pigs, which are fatter and have higher amounts of intramuscular fat than their LOW counterparts. Paradoxically, lipolytic genes also showed increased mRNA levels in the HIGH group suggesting the existence of a cycle where triacylglycerols are continuously synthesized and degraded. Several genes related to the insulin-signalling pathway, that is usually impaired in obese humans, were also upregulated. Finally, genes related to antigen-processing and presentation were downregulated in the HIGH group. CONCLUSION: Our data suggest that selection for increasing intramuscular fat content in pigs would lead to a shift but not a disruption of the metabolic homeostasis of muscle cells. Future studies on the post-translational changes affecting protein activity or expression as well as information about protein location within the cell would be needed to to elucidate the effects of lipid deposition on muscle metabolism in pigs.

Interobserver agreement and validity of bedside 'positive signs' for functional weakness, sensory and gait disorders in conversion disorder: a pilot study.

BACKGROUND: Conversion disorder (CD) is no longer a diagnosis of exclusion. The new DSM-V criteria highlight the importance of 'positive signs' on neurological examination. Only few signs have been validated, and little is known about their reliability. OBJECTIVE: The aim was to examine the clinical value of bedside positive signs in the diagnosis of CD presenting with weakness, gait or sensory symptoms by assessing their specificity, sensitivity and their inter-rater reliability. PATIENTS AND METHODS: Standardised video recorded neurological examinations were performed in 20 consecutive patients with CD and 20 'organic' controls. Ten previously validated sensory and motor signs were grouped in a scale. Thirteen additional motor/sensory 'positive signs', 14 gait patterns and 1 general sign were assessed in a pilot validation study. In addition, two blinded independent neurologists rated the video recordings to assess the inter-rater reliability (Cohen's κ) of each sign. RESULTS: A score of ≥4/14 on the sensory motor scale showed a 100% specificity (CI 85 to 100) and a 95% sensitivity (CI 85 to 100). Among the additional tested signs, 10 were significantly more frequent in CD than controls. The interobserver agreement was acceptable for 23/38 signs (2 excellent, 10 good, 11 moderate). CONCLUSIONS: Our study confirms that six bedside 'positive signs' are highly specific for CD with good-excellent inter-rater reliability; we propose to consider them as 'highly reliable signs'. In addition 13 signs could be considered as 'reliable signs' and six further signs as 'suggestive signs' while all others should be used with caution until further validation is available.