230 research outputs found

    Swaying is a mutant allele of the proto-oncogene Wnt-1

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    Journal ArticleMice homozygous for the recessive mutation swaying (SW) are characterized by ataxia and hypertonia, attributed to the malformation of anterior regions of the cerebellum. We show that SW is a deletion of a single base pair from the proto-oncogene Wnf-1. The deletion is predicted to cause premature termination of translation, eliminating the carboxy-terminal half of the Writ-1 protein. Histological examination shows that SW is phenotypically identical to a previously described writ-1 mutation introduced into mice by gene targeting

    Automated Meteor Fluxes with a Wide-Field Meteor Camera Network

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    Within NASA, the Meteoroid Environment Office (MEO) is charged to monitor the meteoroid environment in near ]earth space for the protection of satellites and spacecraft. The MEO has recently established a two ]station system to calculate automated meteor fluxes in the millimeter ]size ]range. The cameras each consist of a 17 mm focal length Schneider lens on a Watec 902H2 Ultimate CCD video camera, producing a 21.7 x 16.3 degree field of view. This configuration has a red ]sensitive limiting meteor magnitude of about +5. The stations are located in the South Eastern USA, 31.8 kilometers apart, and are aimed at a location 90 km above a point 50 km equidistant from each station, which optimizes the common volume. Both single station and double station fluxes are found, each having benefits; more meteors will be detected in a single camera than will be seen in both cameras, producing a better determined flux, but double station detections allow for non ]ambiguous shower associations and permit speed/orbit determinations. Video from the cameras are fed into Linux computers running the ASGARD (All Sky and Guided Automatic Real ]time Detection) software, created by Rob Weryk of the University of Western Ontario Meteor Physics Group. ASGARD performs the meteor detection/photometry, and invokes the MILIG and MORB codes to determine the trajectory, speed, and orbit of the meteor. A subroutine in ASGARD allows for the approximate shower identification in single station meteors. The ASGARD output is used in routines to calculate the flux in units of #/sq km/hour. The flux algorithm employed here differs from others currently in use in that it does not assume a single height for all meteors observed in the common camera volume. In the MEO system, the volume is broken up into a set of height intervals, with the collecting areas determined by the radiant of active shower or sporadic source. The flux per height interval is summed to obtain the total meteor flux. As ASGARD also computes the meteor mass from the photometry, a mass flux can be also calculated. Weather conditions in the southeastern United States are seldom ideal, which introduces the difficulty of a variable sky background. First a weather algorithm indicates if sky conditions are clear enough to calculate fluxes, at which point a limiting magnitude algorithm is employed. The limiting magnitude algorithm performs a fit of stellar magnitudes vs camera intensities. The stellar limiting magnitude is derived from this and easily converted to a limiting meteor magnitude for the active shower or sporadic source

    Orbit determination of space objects based on sparse optical data

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    While building up a catalog of Earth orbiting objects, if the available optical observations are sparse, not deliberate follow ups of specific objects, no orbit determination is possible without previous correlation of observations obtained at different times. This correlation step is the most computationally intensive, and becomes more and more difficult as the number of objects to be discovered increases. In this paper we tested two different algorithms (and the related prototype software) recently developed to solve the correlation problem for objects in geostationary orbit (GEO), including the accurate orbit determination by full least squares solutions with all six orbital elements. Because of the presence in the GEO region of a significant subpopulation of high area to mass objects, strongly affected by non-gravitational perturbations, it was actually necessary to solve also for dynamical parameters describing these effects, that is to fit between 6 and 8 free parameters for each orbit. The validation was based upon a set of real data, acquired from the ESA Space Debris Telescope (ESASDT) at the Teide observatory (Canary Islands). We proved that it is possible to assemble a set of sparse observations into a set of objects with orbits, starting from a sparse time distribution of observations, which would be compatible with a survey capable of covering the region of interest in the sky just once per night. This could result in a significant reduction of the requirements for a future telescope network, with respect to what would have been required with the previously known algorithm for correlation and orbit determination.Comment: 20 pages, 8 figure

    Video gaming in a hyperconnected world: A cross-sectional study of heavy gaming, problematic gaming symptoms, and online socializing in adolescents

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    Aims Examining online social interactions along with patterns of video gaming behaviors and game addiction symptoms has the potential to enrich our understanding of disorders related to excessive video game play. Methods We performed latent class analysis in a sample of 9733 adolescents based on heavy use of games, social networking and instant messaging, and game addiction symptoms. We used latent class regression to determine associations between classes, psychosocial well-being and friendship quality. Results We identified two types of heavy gaming classes that differed in probability of online social interaction. Classes with more online social interaction reported fewer problematic gaming symptoms than those with less online social interaction. Most adolescents estimated to be in heavy gaming classes had more depressive symptoms than normative classes. Male non-social gamers had more social anxiety. Female social gamers had less social anxiety and loneliness, but lower self-esteem. Friendship quality attenuated depression in some male social gamers, but strengthened associations with loneliness in some male non-social gamers. Conclusions In adolescents, symptoms of video game addiction depend not only on video game play but also on concurrent levels of online communication, and those who are very socially active online report fewer symptoms of game addiction

    REGULATION OF PROSTAGLANDIN GENERATION IN CARRAGEENAN-INDUCED PLEURISY BY INDUCIBLE NITRIC OXIDE SYNTHASE IN KNOCKOUT MICE

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    In the present study, by comparing the responses in wild-type mice (iNOSWT) and mice lacking (iNOSKO) the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the correlation between endogenous nitric oxide (NO) and prostaglandin (PG) generation in carrageenan-induced pleurisy. The inflammatory response in iNOSKO mice was significantly reduced in respect to iNOSWT animals, as demonstrated by the exudate volume (-63%) and numbers of infiltrating cells (-62%). The levels of NOx in the pleural exudate from carrageenan-treated mice were significantly (p < 0.01) decreased in iNOSKO mice (16 ± 7.6 nmoles/mice) compared to iNOSWT animals (133 ± 9 nmoles/mice). Similarly, the amounts of PGE2 in the pleural exudates of carrageenan-treated animals were significantly (p < 0.01) lower in iNOSKO compared to iNOSWT mice (120 ± 20 pg/mice vs. 308 ± 51 pg/mice). Also the amounts of 6-keto-PGF1α produced by lungs from carrageenan-treated iNOSKO mice (1.01 ± 0.10 ng/tissue mg) were significantly (p < 0.01) reduced compared to iNOSWT carrageenan-treated mice (2.1 ± 0.09 ng/tissue mg). In conclusion our results confirm, by the use of iNOSKO mice that in carrageenan-induced pleurisy NO positively modulates PG biosynthesis

    Isolation of single circulating trophoblasts from maternal circulation for noninvasive fetal copy number variant profiling

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    ObjectiveTo develop a multi-step workflow for the isolation of circulating extravillous trophoblasts (cEVTs) by describing the key steps enabling a semi-automated process, including a proprietary algorithm for fetal cell origin genetic confirmation and copy number variant (CNV) detection. MethodsDetermination of the limit of detection (LoD) for submicroscopic CNV was performed by serial experiments with genomic DNA and single cells from Coriell cell line biobank with known imbalances of different sizes. A pregnancy population of 372 women was prospectively enrolled and blindly analyzed to evaluate the current workflow. ResultsAn LoD of 800 Kb was demonstrated with Coriell cell lines. This level of resolution was confirmed in the clinical cohort with the identification of a pathogenic CNV of 800 Kb, also detected by chromosomal microarray. The mean number of recovered cEVTs was 3.5 cells per sample with a significant reverse linear trend between gestational age and cEVT recovery rate and number of recovered cEVTs. In twin pregnanices, evaluation of zygosity, fetal sex and copy number profiling was performed in each individual cell. ConclusionOur semi-automated methodology for the isolation and single-cell analysis of cEVTS supports the feasibility of a cell-based noninvasive prenatal test for fetal genomic profiling. © 2022 A. Menarini Biomarkers Singapore Pte Ltd. Prenatal Diagnosis published by John Wiley &amp; Sons Ltd

    Patterns and predictors of family environment among adolescents at high and low risk for familial bipolar disorder

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    Children's perceptions are important to understanding family environment in the bipolar disorder (BD) high-risk context. Our objectives were to empirically derive patterns of offspring-perceived family environment, and to test the association of family environment with maternal or paternal BD accounting for offspring BD and demographic characteristics. Participants aged 12–21 years (266 offspring of a parent with BD, 175 offspring of a parent with no psychiatric history) were recruited in the US and Australia. We modeled family environment using latent profile analysis based on offspring reports on the Conflict Behavior Questionnaire, Family Adaptability and Cohesion Evaluation Scales, and Home Environment Interview for Children. Parent diagnoses were based on the Diagnostic Interview for Genetic Studies and offspring diagnoses were based on the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Latent class regression was used to test associations of diagnosis and family environment. Two-thirds of all offspring perceived well-functioning family environment, characterized by nurturance, flexibility, and low conflict. Two ‘conflict classes’ perceived family environments low in flexibility and cohesion, with substantial separation based on high conflict with the father (High Paternal Conflict), or very high conflict and rigidity and low warmth with the mother (High Maternal Conflict). Maternal BD was associated with offspring perceiving High Maternal Conflict (OR 2.8, p = 0.025). Clinical care and psychosocial supports for mothers with BD should address family functioning, with attention to offspring perceptions of their wellbeing. More research is needed on the effect of paternal BD on offspring and family dynamics

    An Optical Survey for mm-Sized Interstellar Meteoroids

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    We report high resolution multi-station observations of meteors by the Canadian Automated Meteor Observatory (CAMO) recorded from June 2009 to August 2010. Our survey has a limiting detection magnitude of +5 mag in R-band, equivalent to a limiting meteoroid mass of ~2*E-7 kg. The high metric trajectory accuracy (of the order of 30 m perpendicular to the solution and 200 m along-track) allows us to determine velocities with average uncertainty of < 1.5% in speed and ~0.4 degr in radiant direction. A total of 1739 meteors had measured orbits. The data has been searched for meteors in hyperbolic orbits, which are potentially of interstellar origin. We found 22 potential hyperbolic meteors among our sample, with only two of them having a speed at least three sigma above the hyperbolic limit. For our one year survey we find no clear evidence of interstellar meteoroids at mm-sizes in a weighted time-area product of ~1*E4 km^2*h. Backward integrations performed for these 22 potentially hyperbolic meteors to check for close encounters with planets show no considerable changes in their orbits. Detailed examination leads us to conclude that our few identified events are most likely the result of measurement error. We find an upper limit of f_ISP < 2*E-4/(km^2*h) for the flux of interstellar meteoroids at Earth with a limiting mass of m > 2*E-7 kg.Comment: 15 pages, 2 figures, accepted by Ap

    Zinc and ageing: third Zincage conference

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    The importance of Zn for optimal functioning of the immune system and antioxidant stress response is well documented. Zn homeostasis influences development and function of immune cells, activity of stress-related and antioxidant proteins [metallothioneins (MT), chaperones, ApoJ, Poly(ADP-Ribose) polymerase-1 (PARP-1) and Methionione Sulfoxide Reductase (Msr), Superoxide Dismutase (SOD)], and helps to maintain genomic integrity and stability. During ageing, the intake of Zn decreases due to inadequate diet and/or intestinal malabsorption, contributing to frailty, general disability and increased incidence of age-related degenerative diseases (cancer, infections and atherosclerosis). Although many factors contributing to Zn deficiency have been identified, the biochemical markers of Zn deficiency as well as the possibility to achieve relevant health benefits through Zn supplementation in the elderly are still a matter for evaluation. Taking into account that Zn homeostasis is regulated by proteins and enzymes for which polymorphisms have been previously found to be associated with successful/unsuccessful ageing, genetic screening might be of added value in evaluating the individual response to Zn supplementation. Biochemical, immunological, dietary and genetic studies aimed at understanding the impact of Zn in healthy ageing, the effect of Zn supplementation in the elderly and finally formulating a rationale for the promotion of correct Zn supplementation were discussed at the international Zincage conference held in Ancona in January 2007

    Skeletal Muscle Mitochondrial Protein Synthesis and Respiration Increase With Low-Load Blood Flow Restricted as Well as High-Load Resistance Training

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    Purpose: It is well established that high-load resistance exercise (HLRE) can stimulate myofibrillar accretion. Additionally, recent studies suggest that HLRE can also stimulate mitochondrial biogenesis and respiratory function. However, in several clinical situations, the use of resistance exercise with high loading may not constitute a viable approach. Low-load blood flow restricted resistance exercise (BFRRE) has emerged as a time-effective low-load alternative to stimulate myofibrillar accretion. It is unknown if BFRRE can also stimulate mitochondrial biogenesis and respiratory function. If so, BFRRE could provide a feasible strategy to stimulate muscle metabolic health.Methods: To study this, 34 healthy previously untrained individuals (24 ± 3 years) participated in BFRRE, HLRE, or non-exercise control intervention (CON) 3 times per week for 6 weeks. Skeletal muscle biopsies were collected; (1) before and after the 6-week intervention period to assess mitochondrial biogenesis and respiratory function and; (2) during recovery from single-bout exercise to assess myocellular signaling events involved in transcriptional regulation of mitochondrial biogenesis. During the 6-week intervention period, deuterium oxide (D2O) was continuously administered to the participants to label newly synthesized skeletal muscle mitochondrial proteins. Mitochondrial respiratory function was assessed in permeabilized muscle fibers with high-resolution respirometry. Mitochondrial content was assessed with a citrate synthase activity assay. Myocellular signaling was assessed with immunoblotting.Results: Mitochondrial protein synthesis rate was higher with BFRRE (1.19%/day) and HLRE (1.15%/day) compared to CON (0.92%/day) (P &lt; 0.05) but similar between exercise groups. Mitochondrial respiratory function increased to similar degree with both exercise regimens and did not change with CON. For instance, coupled respiration supported by convergent electron flow from complex I and II increased 38% with BFRRE and 24% with HLRE (P &lt; 0.01). Training did not alter citrate synthase activity compared to CON. BFRRE and HLRE elicited similar myocellular signaling responses.Conclusion: These results support recent findings that resistance exercise can stimulate mitochondrial biogenesis and respiratory function to support healthy skeletal muscle and whole-body metabolism. Intriquingly, BFRRE produces similar mitochondrial adaptations at a markedly lower load, which entail great clinical perspective for populations in whom exercise with high loading is untenable
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