A common variant associated with dyslexia reduces expression of the KIAA0319 gene

This work was supported by the Wellcome Trust (MYD, SP, TSS, JCK, RWM, PC, SB, and APM), the Intramural Research Programs of the National Human Genome Research Institute (MYD and EDG) and National Cancer Institute (MPO), and the NIH/Ox-Cam Graduate Partnership Program (MYD).Numerous genetic association studies have implicated the KIAA0319 gene on human chromosome 6p22 in dyslexia susceptibility. The causative variant(s) remains unknown but may modulate gene expression, given that (1) a dyslexia-associated haplotype has been implicated in the reduced expression of KIAA0319, and (2) the strongest association has been found for the region spanning exon 1 of KIAA0319. Here, we test the hypothesis that variant(s) responsible for reduced KIAA0319 expression resides on the risk haplotype close to the gene's transcription start site. We identified seven single-nucleotide polymorphisms on the risk haplotype immediately upstream of KIAA0319 and determined that three of these are strongly associated with multiple reading-related traits. Using luciferase-expressing constructs containing the KIAA0319 upstream region, we characterized the minimal promoter and additional putative transcriptional regulator regions. This revealed that the minor allele of rs9461045, which shows the strongest association with dyslexia in our sample (max p-value = 0.0001), confers reduced luciferase expression in both neuronal and non-neuronal cell lines. Additionally, we found that the presence of this rs9461045 dyslexia-associated allele creates a nuclear protein-binding site, likely for the transcriptional silencer OCT-1. Knocking down OCT-1 expression in the neuronal cell line SHSY5Y using an siRNA restores KIAA0319 expression from the risk haplotype to nearly that seen from the non-risk haplotype. Our study thus pinpoints a common variant as altering the function of a dyslexia candidate gene and provides an illustrative example of the strategic approach needed to dissect the molecular basis of complex genetic traits.PostprintPeer reviewe

Impartiality and infectious disease: Prioritizing individuals versus the collective in antibiotic prescription

Antimicrobial resistance (AMR) is a global public health disaster driven largely by antibiotic use in human health care. Doctors considering whether to prescribe antibiotics face an ethical conflict between upholding individual patient health and advancing public health aims. Existing literature mainly examines whether patients awaiting consultations desire or expect to receive antibiotic prescriptions, but does not report views of the wider public regarding conditions under which doctors should prescribe antibiotics. It also does not explore the ethical significance of public views or their sensitivity to awareness of AMR risks or the standpoint (self-interested or impartial) taken by participants. Methods: An online survey was conducted with a sample of the U.S. public (n = 158). Participants were asked to indicate what relative priority should be given to individual patients and society-at-large from various standpoints and in various contexts, including antibiotic prescription. Results: Of the participants, 50.3% thought that doctors should generally prioritize individual patients over society, whereas 32.0% prioritized society over individual patients. When asked in the context of AMR, 39.2% prioritized individuals whereas 45.5% prioritized society. Participants were significantly less willing to prioritize society over individuals when they themselves were the patient, both in general (p = .001) and in relation to AMR specifically (p = .006). Conclusions: Participants’ attitudes were more oriented to society and sensitive to collective responsibility when informed about the social costs of antibiotic use and when considered from a third-person rather than first-person perspective. That is, as participants came closer to taking the perspective of an informed and impartial “ideal observer,” their support for prioritizing society increased. Our findings suggest that, insofar as antibiotic policies and practices should be informed by attitudes that are impartial and well-informed, there is significant support for prioritizing society

Heterogeneous Relational Databases for a Grid-enabled Analysis Environment

Grid based systems require a database access mechanism that can provide seamless homogeneous access to the requested data through a virtual data access system, i.e. a system which can take care of tracking the data that is stored in geographically distributed heterogeneous databases. This system should provide an integrated view of the data that is stored in the different repositories by using a virtual data access mechanism, i.e. a mechanism which can hide the heterogeneity of the backend databases from the client applications. This paper focuses on accessing data stored in disparate relational databases through a web service interface, and exploits the features of a Data Warehouse and Data Marts. We present a middleware that enables applications to access data stored in geographically distributed relational databases without being aware of their physical locations and underlying schema. A web service interface is provided to enable applications to access this middleware in a language and platform independent way. A prototype implementation was created based on Clarens [4], Unity [7] and POOL [8]. This ability to access the data stored in the distributed relational databases transparently is likely to be a very powerful one for Grid users, especially the scientific community wishing to collate and analyze data distributed over the Grid

Responses of stomatal features and photosynthesis to porewater N enrichment and elevated atmospheric CO2 in Phragmites australis, the common reed

PREMISE Biological invasions increasingly threaten native biodiversity and ecosystem services. One notable example is the common reed, Phragmites australis, which aggressively invades North American salt marshes. Elevated atmospheric CO2 and nitrogen pollution enhance its growth and facilitate invasion because P. australis responds more strongly to these enrichments than do native species. We investigated how modifications to stomatal features contribute to strong photosynthetic responses to CO2 and nitrogen enrichment in P. australis by evaluating stomatal shifts under experimental conditions and relating them to maximal stomatal conductance (g(wmax)) and photosynthetic rates.METHODS Plants were grown in situ in open-top chambers under ambient and elevated atmospheric CO2 (eCO(2)) and porewater nitrogen (N-enr) in a Chesapeake Bay tidal marsh. We measured light-saturated carbon assimilation rates (A(sat)) and stomatal characteristics, from which we calculated g(wmax) and determined whether CO2 and N-enr altered the relationship between g(wmax) and A(sat).RESULTS eCO(2) and N-enr enhanced both g(wmax) and A(sat), but to differing degrees; g(wmax) was more strongly influenced by N-enr through increases in stomatal density while A(sat) was more strongly stimulated by eCO(2). There was a positive relationship between g(wmax) and A(sat) that was not modified by eCO(2) or N-enr, individually or in combination.CONCLUSIONS Changes in stomatal features co-occur with previously described responses of P. australis to eCO(2) and N-enr. Complementary responses of stomatal length and density to these global change factors may facilitate greater stomatal conductance and carbon gain, contributing to the invasiveness of the introduced lineage

Electrochemical properties of micro-batteries with single NCM-111 secondary particles as cathode

Although lithium ion batteries (LIB) are already used in numerous applications, e.g. as power source in portable devices, the optimization of the battery performance, such as life-time, cyclability and energy density, is of large interest for using LIBs in e.g. electrical vehicles or temporary storage systems for renewable energy sources. Typically, the performance of the cathode active material is investigated using composite electrodes. Advanced composite electrodes consist of a complex architecture with comparably large secondary particles (10 µm - 30 µm) of the active material built up from nanometer sized primary particles. Furthermore, they also contain additives influencing the electrochemical properties of the composite electrode. To avoid such influences and to further optimize the performance of the cathode’s active material a detailed understanding of the impact of the cathode architecture on the ionic and electronic transport processes is necessary. Please click Additional Files below to see the full abstract

Graphene-coated Rayleigh SAW resonators for NO2detection

This paper describes the development of a novel low-cost Rayleigh Surface Acoustic Wave Resonator (SAWR) device coated with a graphene layer that is capable of detecting PPM levels of NO2 in air. The sensor comprises two 262 MHz ST-cut quartz based Rayleigh SAWRs arranged in a dual oscillator configuration; where one resonator is coated with gas-sensitive graphene, and the other left uncoated to act as a reference. An array of NMP-dispersed exfoliated reduced graphene oxide dots was deposited in the active area inside the SAWR IDTs by a non-contacting, micro ink-jet printing system. An automated Mass Flow Controller system has been developed that delivers gases to the SAWR sensors with circuitry for excitation, amplification, buffering and signal read-out. This SAW-based graphene sensor has sensitivity to NO2 of ca. 25 Hz/ppm and could be implemented in a low-power low-cost gas sensor

Synthesis and Characterization of Metallopolymer Networks featuring Triple Shape-Memory Ability Based on Different Reversible Metal Complexes

This study presents the synthesis and characterization of metallopolymer networks with a triple shape-memory ability. A covalently crosslinked polymer network featuring two different additional ligands in its side chains is synthesized via free radical polymerization (FRP). The subsequent addition of different metal salts leads to the selective formation of complexes with two different association constants ( K a ), proven via isothermal titration calorimetry (ITC). Those two supramolecular crosslinks feature different activation temperatures and can act as two individual switching units enabling the fixation and recovery of two temporary shapes. The presented samples were investigated in a detailed fashion via differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and FT-Raman spectroscopy. Furthermore, thermo-mechanical analyses (TMA) revealed excellent dual and triple shape-memory abilities of the presented metallopolymer networks

Static Disorder in Excitation Energies of the Fenna-Matthews-Olson Protein: Structure-Based Theory Meets Experiment

Inhomogeneous broadening of optical lines of the Fenna-Matthews-Olson (FMO) light-harvesting protein is investigated by combining a Monte Carlo sampling of low-energy conformational substates of the protein with a quantum chemical/electrostatic calculation of local transition energies (site energies) of the pigments. The good agreement between the optical spectra calculated for the inhomogeneous ensemble and the experimental data demonstrates that electrostatics is the dominant contributor to static disorder in site energies. Rotamers of polar amino acid side chains are found to cause bimodal distribution functions of site energy shifts, which can be probed by hole burning and single-molecule spectroscopy. When summing over the large number of contributions, the resulting distribution functions of the site energies become Gaussians, and the correlations in site energy fluctuations at different sites practically average to zero. These results demonstrate that static disorder in the FMO protein is in the realm of the central limit theorem of statistics. © 2020 American Chemical Society