Wdr18 Is Required for Kupffer's Vesicle Formation and Regulation of Body Asymmetry in Zebrafish

Correct specification of the left-right (L-R) axis is important for organ morphogenesis. Conserved mechanisms involving cilia rotation inside node-like structures and asymmetric Nodal signaling in the lateral plate mesoderm (LPM), which are important symmetry-breaking events, have been intensively studied. In zebrafish, the clustering and migration of dorsal forerunner cells (DFCs) is critical for the formation of the Kuppfer's vesicle (KV). However, molecular events underlying DFC clustering and migration are less understood. The WD-repeat proteins function in a variety of biological processes, including cytoskeleton assembly, intracellular trafficking, mRNA splicing, transcriptional regulation and cell migration. However, little is known about the function of WD-repeat proteins in L-R asymmetry determination. Here, we report the identification and functional analyses of zebrafish wdr18, a novel gene that encodes a WD-repeat protein that is highly conserved among vertebrate species. wdr18 was identified from a Tol2 transposon-mediated enhancer trap screen. Follow-up analysis of wdr18 mRNA expression showed that it was detected in DFCs or the KV progenitor cells and later in the KV at early somitogenesis stages. Morpholino knockdown of wdr18 resulted in laterality defects in the visceral organs, which were preceded by the mis-expression of Nodal-related genes, including spaw and pitx2. Examination of morphants at earlier stages revealed that the KV had fewer and shorter cilia which are immotile and a smaller cavity. We further investigated the organization of DFCs in wdr18 morphant embryos using ntl and sox17 as specific markers and found that the clustering and migration of DFC was altered, leading to a disorganized KV. Finally, through a combination of wdr18 and itgb1b morpholino injections, we provided evidence that wdr18 and itgb1b genetically interact in the laterality determination process. Thus, we reveal a new and essential role for WD-repeat proteins in the determination and regulation of L-R asymmetry and propose a potential mechanism for wdr18 in the regulation of DFC clustering and migration and KV formation

Nature and mental health: An ecosystem service perspective

This is the final version. Available on open access from American Association for the Advancement of Science via the DOI in this recordData and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.A growing body of empirical evidence is revealing the value of nature experience for mental health. With rapid urbanization and declines in human contact with nature globally, crucial decisions must be made about how to preserve and enhance opportunities for nature experience. Here, we first provide points of consensus across the natural, social, and health sciences on the impacts of nature experience on cognitive functioning, emotional well-being, and other dimensions of mental health. We then show how ecosystem service assessments can be expanded to include mental health, and provide a heuristic, conceptual model for doing so.Doug Walker Endowed ProfessorshipCraig McKibben and Sarah MernerJohn MillerMarianne and Marcus Wallenberg FoundationWinslow FoundationGeorge Rudolf Fellowship FundVictoria and David Rogers FundMr. & Mrs. Dean A. McGee Fun

Analytic philosophy for biomedical research: the imperative of applying yesterday's timeless messages to today's impasses

The mantra that "the best way to predict the future is to invent it" (attributed to the computer scientist Alan Kay) exemplifies some of the expectations from the technical and innovative sides of biomedical research at present. However, for technical advancements to make real impacts both on patient health and genuine scientific understanding, quite a number of lingering challenges facing the entire spectrum from protein biology all the way to randomized controlled trials should start to be overcome. The proposal in this chapter is that philosophy is essential in this process. By reviewing select examples from the history of science and philosophy, disciplines which were indistinguishable until the mid-nineteenth century, I argue that progress toward the many impasses in biomedicine can be achieved by emphasizing theoretical work (in the true sense of the word 'theory') as a vital foundation for experimental biology. Furthermore, a philosophical biology program that could provide a framework for theoretical investigations is outlined

Infectious Offspring: How Birds Acquire and Transmit an Avian Polyomavirus in the Wild

Detailed patterns of primary virus acquisition and subsequent dispersal in wild vertebrate populations are virtually absent. We show that nestlings of a songbird acquire polyomavirus infections from larval blowflies, common nest ectoparasites of cavity-nesting birds, while breeding adults acquire and renew the same viral infections via cloacal shedding from their offspring. Infections by these DNA viruses, known potential pathogens producing disease in some bird species, therefore follow an ‘upwards vertical’ route of an environmental nature mimicking horizontal transmission within families, as evidenced by patterns of viral infection in adults and young of experimental, cross-fostered offspring. This previously undescribed route of viral transmission from ectoparasites to offspring to parent hosts may be a common mechanism of virus dispersal in many taxa that display parental care

Dependence of Bacterial Chemotaxis on Gradient Shape and Adaptation Rate

Simulation of cellular behavior on multiple scales requires models that are sufficiently detailed to capture central intracellular processes but at the same time enable the simulation of entire cell populations in a computationally cheap way. In this paper we present RapidCell, a hybrid model of chemotactic Escherichia coli that combines the Monod-Wyman-Changeux signal processing by mixed chemoreceptor clusters, the adaptation dynamics described by ordinary differential equations, and a detailed model of cell tumbling. Our model dramatically reduces computational costs and allows the highly efficient simulation of E. coli chemotaxis. We use the model to investigate chemotaxis in different gradients, and suggest a new, constant-activity type of gradient to systematically study chemotactic behavior of virtual bacteria. Using the unique properties of this gradient, we show that optimal chemotaxis is observed in a narrow range of CheA kinase activity, where concentration of the response regulator CheY-P falls into the operating range of flagellar motors. Our simulations also confirm that the CheB phosphorylation feedback improves chemotactic efficiency by shifting the average CheY-P concentration to fit the motor operating range. Our results suggest that in liquid media the variability in adaptation times among cells may be evolutionary favorable to ensure coexistence of subpopulations that will be optimally tactic in different gradients. However, in a porous medium (agar) such variability appears to be less important, because agar structure poses mainly negative selection against subpopulations with low levels of adaptation enzymes. RapidCell is available from the authors upon request

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Short-term acclimation in adults does not predict offspring acclimation potential to hypoxia

Abstract The prevalence of hypoxic areas in coastal waters is predicted to increase and lead to reduced biodiversity. While the adult stages of many estuarine invertebrates can cope with short periods of hypoxia, it remains unclear whether that ability is present if animals are bred and reared under chronic hypoxia. We firstly investigated the effect of moderate, short-term environmental hypoxia (40% air saturation for one week) on metabolic performance in adults of an estuarine amphipod, and the fitness consequences of prolonged exposure. We then reared the offspring of hypoxia-exposed parents under hypoxia, and assessed their oxyregulatory ability under declining oxygen tensions as juveniles and adults. Adults from the parental generation were able to acclimate their metabolism to hypoxia after one week, employing mechanisms typically associated with prolonged exposure. Their progeny, however, did not develop the adult pattern of respiratory regulation when reared under chronic hypoxia, but instead exhibited a poorer oxyregulatory ability than their parents. We conclude that species apparently hypoxia-tolerant when tested in short-term experiments, could be physiologically compromised as adults if they develop under hypoxia. Consequently, we propose that the increased prevalence of hypoxia in coastal regions will have marked effects in some species currently considered hypoxia tolerant

Recursive partitioning analysis of prognostic factors in WHO grade III glioma patients treated with radiotherapy or radiotherapy plus chemotherapy

<p>Abstract</p> <p>Background</p> <p>We evaluated the hierarchical risk groups for the estimated survival of WHO grade III glioma patients using recursive partitioning analysis (RPA). To our knowledge, this is the first study to address the results of RPA specifically for WHO grade III gliomas.</p> <p>Methods</p> <p>A total of 133 patients with anaplastic astrocytoma (AA, n = 56), anaplastic oligodendroglioma (AO, n = 67), or anaplastic oligoastrocytoma (AOA, n = 10) were included in the study. These patients were treated with either radiotherapy alone or radiotherapy followed by PCV chemotherapy after surgery. Five prognostic factors, including histological subsets, age, performance status, extent of resection, and treatment modality were incorporated into the RPA. The final nodes of RPA were grouped according to their survival times, and the Kaplan-Meier graphs are presented as the final set of prognostic groups.</p> <p>Results</p> <p>Four risk groups were defined based on the clinical prognostic factors excluding age, and split variables were all incorporated into the RPA. Survival analysis showed significant differences in mean survival between the different groups: 163.4 months (95% CI: 144.9-182.0), 109.5 months (86.7-132.4), 66.6 months (50.8-82.4), and 27.7 months (16.3-39.0), respectively, from the lowest to the highest risk group (p = 0.00).</p> <p>Conclusion</p> <p>The present study shows that RPA grouping with clinical prognostic factors can successfully predict the survival of patients with WHO grade III glioma.</p