Spina bifida-predisposing heterozygous mutations in Planar Cell Polarity genes and Zic2 reduce bone mass in young mice

Fractures are a common comorbidity in children with the neural tube defect (NTD) spina bifida. Mutations in the Wnt/planar cell polarity (PCP) pathway contribute to NTDs in humans and mice, but whether this pathway independently determines bone mass is poorly understood. Here, we first confirmed that core Wnt/PCP components are expressed in osteoblasts and osteoclasts in vitro. In vivo, we performed detailed µCT comparisons of bone structure in tibiae from young male mice heterozygous for NTD-associated mutations versus WT littermates. PCP signalling disruption caused by Vangl2 (Vangl2Lp/+) or Celsr1 (Celsr1Crsh/+) mutations significantly reduced trabecular bone mass and distal tibial cortical thickness. NTD-associated mutations in non-PCP transcription factors were also investigated. Pax3 mutation (Pax3Sp2H/+) had minimal effects on bone mass. Zic2 mutation (Zic2Ku/+) significantly altered the position of the tibia/fibula junction and diminished cortical bone in the proximal tibia. Beyond these genes, we bioinformatically documented the known extent of shared genetic networks between NTDs and bone properties. 46 genes involved in neural tube closure are annotated with bone-related ontologies. These findings document shared genetic networks between spina bifida risk and bone structure, including PCP components and Zic2. Genetic variants which predispose to spina bifida may therefore independently diminish bone mass

Taking stock of current societal, political and academic stakeholders in the Canadian healthcare knowledge translation agenda

<p>Abstract</p> <p>Background</p> <p>In the past 15 years, knowledge translation in healthcare has emerged as a multifaceted and complex agenda. Theoretical and polemical discussions, the development of a science to study and measure the effects of translating research evidence into healthcare, and the role of key stakeholders including academe, healthcare decision-makers, the public, and government funding bodies have brought scholarly, organizational, social, and political dimensions to the agenda.</p> <p>Objective</p> <p>This paper discusses the current knowledge translation agenda in Canadian healthcare and how elements in this agenda shape the discovery and translation of health knowledge.</p> <p>Discussion</p> <p>The current knowledge translation agenda in Canadian healthcare involves the influence of values, priorities, and people; stakes which greatly shape the discovery of research knowledge and how it is or is not instituted in healthcare delivery. As this agenda continues to take shape and direction, ensuring that it is accountable for its influences is essential and should be at the forefront of concern to the Canadian public and healthcare community. This transparency will allow for scrutiny, debate, and improvements in health knowledge discovery and health services delivery.</p

Increasing Costs Due to Ocean Acidification Drives Phytoplankton to Be More Heavily Calcified: Optimal Growth Strategy of Coccolithophores

Ocean acidification is potentially one of the greatest threats to marine ecosystems and global carbon cycling. Amongst calcifying organisms, coccolithophores have received special attention because their calcite precipitation plays a significant role in alkalinity flux to the deep ocean (i.e., inorganic carbon pump). Currently, empirical effort is devoted to evaluating the plastic responses to acidification, but evolutionary considerations are missing from this approach. We thus constructed an optimality model to evaluate the evolutionary response of coccolithophorid life history, assuming that their exoskeleton (coccolith) serves to reduce the instantaneous mortality rates. Our model predicted that natural selection favors constructing more heavily calcified exoskeleton in response to increased acidification-driven costs. This counter-intuitive response occurs because the fitness benefit of choosing a better-defended, slower growth strategy in more acidic conditions, outweighs that of accelerating the cell cycle, as this occurs by producing less calcified exoskeleton. Contrary to the widely held belief, the evolutionarily optimized population can precipitate larger amounts of CaCO3 during the bloom in more acidified seawater, depending on parameter values. These findings suggest that ocean acidification may enhance the calcification rates of marine organisms as an adaptive response, possibly accompanied by higher carbon fixation ability. Our theory also provides a compelling explanation for the multispecific fossil time-series record from ∼200 years ago to present, in which mean coccolith size has increased along with rising atmospheric CO2 concentration

Whale, whale, everywhere: increasing abundance of western South Atlantic humpback whales (Megaptera novaeangliae) in their wintering grounds

The western South Atlantic (WSA) humpback whale population inhabits the coast of Brazil during the breeding and calving season in winter and spring. This population was depleted to near extinction by whaling in the mid-twentieth century. Despite recent signs of recovery, increasing coastal and offshore development pose potential threats to these animals. Therefore, continuous monitoring is needed to assess population status and support conservation strategies. The aim of this work was to present ship-based line-transect estimates of abundance for humpback whales in their WSA breeding ground and to investigate potential changes in population size. Two cruises surveyed the coast of Brazil during August-September in 2008 and 2012. The area surveyed in 2008 corresponded to the currently recognized population breeding area; effort in 2012 was limited due to unfavorable weather conditions. WSA humpback whale population size in 2008 was estimated at 16,410 (CV = 0.228, 95% CI = 10,563–25,495) animals. In order to compare abundance between 2008 and 2012, estimates for the area between Salvador and Cabo Frio, which were consistently covered in the two years, were computed at 15,332 (CV = 0.243, 95% CI = 9,595–24,500) and 19,429 (CV = 0.101, 95% CI = 15,958–23,654) whales, respectively. The difference in the two estimates represents an increase of 26.7% in whale numbers in a 4-year period. The estimated abundance for 2008 is considered the most robust for the WSA humpback whale population because the ship survey conducted in that year minimized bias from various sources. Results presented here indicate that in 2008, the WSA humpback whale population was at least around 60% of its estimated pre-modern whaling abundance and that it may recover to its pre-exploitation size sooner than previously estimated.Publisher PDFPeer reviewe

Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702

We compared the efficacy and the safety of a carboplatin plus etoposide regimen (CE) vs split doses of cisplatin plus etoposide (SPE) in elderly or poor-risk patients with extensive disease small-cell lung cancer (ED-SCLC). Eligibility criteria included: untreated ED-SCLC; age ⩾70 and performance status 0–2, or age <70 and PS 3. The CE arm received carboplatin area under the curve of five intravenously (IV) on day 1 and etoposide 80 mg m−2 IV on days 1–3. The SPE arm received cisplatin 25 mg m−2 IV on days 1–3 and etoposide 80 mg m−2 IV on days 1–3. Both regimens were given with granulocyte colony-stimulating factor support in a 21–28 day cycle for four courses. A total of 220 patients were randomised. Median age was 74 years and 74% had a PS of 0 or 1. Major grade 3–4 toxicities were (%CE/%SPE): leucopenia 54/51, neutropenia 95/90, thrombocytopenia 56/16, infection 7/6. There was no significant difference (CE/SPE) in the response rate (73/73%) and overall survival (median 10.6/9.9 mo; P=0.54). Palliation scores were very similar between the arms. Although the SPE regimen is still considered to be the standard treatment in elderly or poor-risk patients with ED-SCLC, the CE regimen can be an alternative for this population considering the risk–benefit balance

What is the role of the film viewer? The effects of narrative comprehension and viewing task on gaze control in film

Film is ubiquitous, but the processes that guide viewers' attention while viewing film narratives are poorly understood. In fact, many film theorists and practitioners disagree on whether the film stimulus (bottom-up) or the viewer (top-down) is more important in determining how we watch movies. Reading research has shown a strong connection between eye movements and comprehension, and scene perception studies have shown strong effects of viewing tasks on eye movements, but such idiosyncratic top-down control of gaze in film would be anathema to the universal control mainstream filmmakers typically aim for. Thus, in two experiments we tested whether the eye movements and comprehension relationship similarly held in a classic film example, the famous opening scene of Orson Welles' Touch of Evil (Welles & Zugsmith, Touch of Evil, 1958). Comprehension differences were compared with more volitionally controlled task-based effects on eye movements. To investigate the effects of comprehension on eye movements during film viewing, we manipulated viewers' comprehension by starting participants at different points in a film, and then tracked their eyes. Overall, the manipulation created large differences in comprehension, but only produced modest differences in eye movements. To amplify top-down effects on eye movements, a task manipulation was designed to prioritize peripheral scene features: a map task. This task manipulation created large differences in eye movements when compared to participants freely viewing the clip for comprehension. Thus, to allow for strong, volitional top-down control of eye movements in film, task manipulations need to make features that are important to narrative comprehension irrelevant to the viewing task. The evidence provided by this experimental case study suggests that filmmakers' belief in their ability to create systematic gaze behavior across viewers is confirmed, but that this does not indicate universally similar comprehension of the film narrative

Developing Literacy Learning Model Based on Multi Literacy, Integrated, and Differentiated Concept at Primary School

The main issue addressed in this research is the low writing skills of primary school students. One of the reasons for this condition is that the existing model of writing literacy learning is not appropriate. The purpose of this study is to explain MID-based literacy teaching model and the impact of the model in increasing primary school students\u27 writing skills. This study used combined methods of exploratory type. The samples were elementary school students coming from six schools with three different characteristics. Based on the data analysis, it can be concluded that the implementation of MID-based literacy learning model has proven to signi cantly contribute to the improvement of students\u27 writing skills. Taking place in all sample schools, the improvement may suggest that the model ts not only to students with high- ability but also those with low-ability. Therefore, the MID-based literacy learning model is needed to improve the ability to write various text types appropriately

Stream denitrification across biomes and its response to anthropogenic nitrate loading

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 452 (2008): 202-205, doi:10.1038/nature06686.Worldwide, anthropogenic addition of bioavailable nitrogen (N) to the biosphere is increasing and terrestrial ecosystems are becoming increasingly N saturated, causing more bioavailable N to enter groundwater and surface waters. Large-scale N budgets show that an average of about 20-25% of the N added to the biosphere is exported from rivers to the ocean or inland basins, indicating substantial sinks for N must exist in the landscape. Streams and rivers may be important sinks for bioavailable N owing to their hydrologic connections with terrestrial systems, high rates of biological activity, and streambed sediment environments that favor microbial denitrification. Here, using data from 15N tracer experiments replicated across 72 streams and 8 regions representing several biomes, we show that total biotic uptake and denitrification of nitrate increase with stream nitrate concentration, but that the efficiency of biotic uptake and denitrification declines as concentration increases, reducing the proportion of instream nitrate that is removed from transport. Total uptake of nitrate was related to ecosystem photosynthesis and denitrification was related to ecosystem respiration. Additionally, we use a stream network model to demonstrate that excess nitrate in streams elicits a disproportionate increase in the fraction of nitrate that is exported to receiving waters and reduces the relative role of small versus large streams as nitrate sinks.Funding for this research was provided by the National Science Foundation

The influence of early aging on eye movements during motor simulation

Movement based interventions such as imagery and action observation are used increasingly to support physical rehabilitation of adults during early aging. The efficacy of these more covert approaches is based on an intuitively appealing assumption that movement execution, imagery and observation share neural substrate; alteration of one influences directly the function of the other two. Using eye movement metrics this paper reports findings that question the congruency of the three conditions. The data reveal that simulating movement through imagery and action observation may offer older adults movement practice conditions that are not constrained by the age-related decline observed in physical conditions. In addition, the findings provide support for action observation as a more effective technique for movement reproduction in comparison to imagery. This concern for imagery was also seen in the less congruent temporal relationship in movement time between imagery and movement execution suggesting imagery inaccuracy in early aging