A Upf3b-mutant mouse model with behavioral and neurogenesis defects.

Nonsense-mediated RNA decay (NMD) is a highly conserved and selective RNA degradation pathway that acts on RNAs terminating their reading frames in specific contexts. NMD is regulated in a tissue-specific and developmentally controlled manner, raising the possibility that it influences developmental events. Indeed, loss or depletion of NMD factors have been shown to disrupt developmental events in organisms spanning the phylogenetic scale. In humans, mutations in the NMD factor gene, UPF3B, cause intellectual disability (ID) and are strongly associated with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia (SCZ). Here, we report the generation and characterization of mice harboring a null Upf3b allele. These Upf3b-null mice exhibit deficits in fear-conditioned learning, but not spatial learning. Upf3b-null mice also have a profound defect in prepulse inhibition (PPI), a measure of sensorimotor gating commonly deficient in individuals with SCZ and other brain disorders. Consistent with both their PPI and learning defects, cortical pyramidal neurons from Upf3b-null mice display deficient dendritic spine maturation in vivo. In addition, neural stem cells from Upf3b-null mice have impaired ability to undergo differentiation and require prolonged culture to give rise to functional neurons with electrical activity. RNA sequencing (RNAseq) analysis of the frontal cortex identified UPF3B-regulated RNAs, including direct NMD target transcripts encoding proteins with known functions in neural differentiation, maturation and disease. We suggest Upf3b-null mice serve as a novel model system to decipher cellular and molecular defects underlying ID and neurodevelopmental disorders

Frame dragging with optical vortices

General Relativistic calculations in the linear regime have been made for electromagnetic beams of radiation known as optical vortices. These exotic beams of light carry a physical quantity known as optical orbital angular momentum (OAM). It is found that when a massive spinning neutral particle is placed along the optical axis, a phenomenon known as inertial frame dragging occurs. Our results are compared with those found previously for a ring laser and an order of magnitude estimate of the laser intensity needed for a precession frequency of 1 Hz is given for these "steady" beams of light.Comment: 13 pages, 2 figure

Housekeeping genes for quantitative expression studies in the three-spined stickleback Gasterosteus aculeatus

Background During the last years the quantification of immune response under immunological challenges, e.g. parasitation, has been a major focus of research. In this context, the expression of immune response genes in teleost fish has been surveyed for scientific and commercial purposes. Despite the fact that it was shown in teleostei and other taxa that the gene for beta-actin is not the most stably expressed housekeeping gene (HKG), depending on the tissue and experimental treatment, the gene has been us Results To establish a reliable method for the measurement of immune gene expression in Gasterosteus aculeatus, sequences from the now available genome database and an EST library of the same species were used to select oligonucleotide primers for HKG, in order to perform quantitative reverse-transcription (RT) PCR. The expression stability of ten candidate reference genes was evaluated in three different tissues, and in five parasite treatment groups, using the three algorithms BestKeeper, geNorm and N Conclusion As they were the most stably expressed genes in all tissues examined, we suggest using the genes for the L13a ribosomal binding protein and ubiquitin as alternative or additional reference genes in expression analysis in Gasterosteus aculeatus.

Surprising dissimilarities in a newly formed pair of 'identical twin' stars

The mass and chemical composition of a star are the primary determinants of its basic physical properties--radius, temperature, luminosity--and how those properties evolve with time. Thus, two stars born at the same time, from the same natal material, and with the same mass are 'identical twins,' and as such might be expected to possess identical physical attributes. We have discovered in the Orion Nebula a pair of stellar twins in a newborn binary star system. Each star in the binary has a mass of 0.41 +/- 0.01 solar masses, identical to within 2 percent. Here we report that these twin stars have surface temperatures that differ by ~300K (~10%), and luminosities that differ by ~50%, both at high confidence level. Preliminary results indicate that the stars' radii also differ, by 5-10%. These surprising dissimilarities suggest that one of the twins may have been delayed by several hundred thousand years in its formation relative to its sibling. Such a delay could only have been detected in a very young, definitively equal-mass binary system3 such as that reported here. Our findings reveal cosmic limits on the age synchronisation of young binary stars, often used as tests for the age calibrations of star-formation models.Comment: Published in Nature, 19 June 200

Variability in gene expression underlies incomplete penetrance

The phenotypic differences between individual organisms can often be ascribed to underlying genetic and environmental variation. However, even genetically identical organisms in homogeneous environments vary, indicating that randomness in developmental processes such as gene expression may also generate diversity. To examine the consequences of gene expression variability in multicellular organisms, we studied intestinal specification in the nematode Caenorhabditis elegans in which wild-type cell fate is invariant and controlled by a small transcriptional network. Mutations in elements of this network can have indeterminate effects: some mutant embryos fail to develop intestinal cells, whereas others produce intestinal precursors. By counting transcripts of the genes in this network in individual embryos, we show that the expression of an otherwise redundant gene becomes highly variable in the mutants and that this variation is subjected to a threshold, producing an ON/OFF expression pattern of the master regulatory gene of intestinal differentiation. Our results demonstrate that mutations in developmental networks can expose otherwise buffered stochastic variability in gene expression, leading to pronounced phenotypic variation.National Institutes of Health (U.S.). Pioneer AwardMathematical Sciences Postdoctoral Research Fellowships (DMS-0603392)National Institutes of Health (U.S.). Ruth L. Kirschstein National Research Service Award (5F32GM080966

Visual Search Strategies of Soccer Players Executing a Power vs. Placement Penalty Kick

Introduction: When taking a soccer penalty kick, there are two distinct kicking techniques that can be adopted; a ‘power’ penalty or a ‘placement’ penalty. The current study investigated how the type of penalty kick being taken affected the kicker’s visual search strategy and where the ball hit the goal (end ball location). Method: Wearing a portable eye tracker, 12 university footballers executed 2 power and placement penalty kicks, indoors, both with and without the presence of a goalkeeper. Video cameras were used to determine initial ball velocity and end ball location. Results: When taking the power penalty, the football was kicked significantly harder and more centrally in the goal compared to the placement penalty. During the power penalty, players fixated on the football for longer and more often at the goalkeeper (and by implication the middle of the goal), whereas in the placement penalty, fixated longer at the goal, specifically the edges. Findings remained consistent irrespective of goalkeeper presence. Discussion/conclusion: Findings indicate differences in visual search strategy and end ball location as a function of type of penalty kick. When taking the placement penalty, players fixated and kicked the football to the edges of the goal in an attempt to direct the ball to an area that the goalkeeper would have difficulty reaching and saving. Fixating significantly longer on the football when taking the power compared to placement penalty indicates a greater importance of obtaining visual information from the football. This can be attributed to ensuring accurate foot-to-ball contact and subsequent generation of ball velocity. Aligning gaze and kicking the football centrally in the goal when executing the power compared to placement penalty may have been a strategy to reduce the risk of kicking wide of the goal altogether

Microbial catabolic activities are naturally selected by metabolic energy harvest rate

The fundamental trade-off between yield and rate of energy harvest per unit of substrate has been largely discussed as a main characteristic for microbial established cooperation or competition. In this study, this point is addressed by developing a generalized model that simulates competition between existing and not experimentally reported microbial catabolic activities defined only based on well-known biochemical pathways. No specific microbial physiological adaptations are considered, growth yield is calculated coupled to catabolism energetics and a common maximum biomass-specific catabolism rate (expressed as electron transfer rate) is assumed for all microbial groups. Under this approach, successful microbial metabolisms are predicted in line with experimental observations under the hypothesis of maximum energy harvest rate. Two microbial ecosystems, typically found in wastewater treatment plants, are simulated, namely: (i) the anaerobic fermentation of glucose and (ii) the oxidation and reduction of nitrogen under aerobic autotrophic (nitrification) and anoxic heterotrophic and autotrophic (denitrification) conditions. The experimentally observed cross feeding in glucose fermentation, through multiple intermediate fermentation pathways, towards ultimately methane and carbon dioxide is predicted. Analogously, two-stage nitrification (by ammonium and nitrite oxidizers) is predicted as prevailing over nitrification in one stage. Conversely, denitrification is predicted in one stage (by denitrifiers) as well as anammox (anaerobic ammonium oxidation). The model results suggest that these observations are a direct consequence of the different energy yields per electron transferred at the different steps of the pathways. Overall, our results theoretically support the hypothesis that successful microbial catabolic activities are selected by an overall maximum energy harvest rate

Locally harvested foods support serum 25-hydroxyvitamin D sufficiency in an indigenous population of Western Alaska

Background: Low serum vitamin D is associated with higher latitude, age, body fat percentage and low intake of fatty fish. Little documentation of vitamin D concentrations is available for Alaska Native populations. Objective: This study was undertaken to investigate serum 25-hydroxyvitamin D (25(OH)D) concentrations of the Yup'ik people of southwestern Alaska in relation to demographic and lifestyle variables, particularly with the use of locally harvested (local) foods. Design: Cross-sectional study. Methods: We estimated 25(OH)D, dietary vitamin D and calcium, percent of energy from local foods and demographic variables in 497 Yup'ik people (43% males) aged 14–92 residing in southwestern Alaska. Sampling was approximately equally divided between synthesizing and non-synthesizing seasons, although the preponderance of samples were drawn during months of increasing daylight. Results: Mean vitamin D intake was 15.1±20.2 µg/d, while local foods accounted for 22.9±17.1% of energy intake. The leading sources of vitamin D were local fish (90.1%) followed by market foods. Mean 25(OH)D concentration was 95.6±40.7 nmol/L. Participants in the upper 50th percentile of 25(OH)D concentration tended to be older, male, of lower body mass index, sampled during the synthesizing season, and among the upper 50th percentile of local food use. Conclusions: A shift away from locally harvested foods will likely increase the risk for serum 25(OH)D insufficiency in this population

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table