The α2δ-like Protein Cachd1 Increases N-type Calcium Currents and Cell Surface Expression and Competes with α2δ-1

Voltage-gated calcium channel auxiliary α2δ subunits are important for channel trafficking and function. Here, we compare the effects of α2δ-1 and an α2δ-like protein called Cachd1 on neuronal N-type (CaV2.2) channels, which are important in neurotransmission. Previous structural studies show the α2δ-1 VWA domain interacting with the first loop in CaV1.1 domain-I via its metal ion-dependent adhesion site (MIDAS) motif and additional Cache domain interactions. Cachd1 has a disrupted MIDAS motif. However, Cachd1 increases CaV2.2 currents substantially (although less than α2δ-1) and increases CaV2.2 cell surface expression by reducing endocytosis. Although the effects of α2δ-1 are abolished by mutation of Asp122 in CaV2.2 domain-I, which mediates interaction with its VWA domain, the Cachd1 responses are unaffected. Furthermore, Cachd1 co-immunoprecipitates with CaV2.2 and inhibits co-immunoprecipitation of α2δ-1 by CaV2.2. Cachd1 also competes with α2δ-1 for effects on trafficking. Thus, Cachd1 influences both CaV2.2 trafficking and function and can inhibit responses to α2δ-1

Quantitative analysis of dribble volumes and rates using three-dimensional reconstruction of X-ray and diffused back-illumination images of diesel sprays

[EN] Post-injection fuel dribble is known to lead to incomplete atomisation and combustion due to the release of slow-moving, and often surface-bound, liquid fuel after the end of injection. This can have a negative effect on engine emissions, performance and injector durability. To better quantify this phenomenon, we developed an image-processing approach to measure the volume of ligaments produced during the end of injection. We applied our processing approach to an Engine Combustion Network 'Spray B' 3-hole injector, using datasets from 220 injections generated by different research groups, to decouple the effect of gas temperature and pressure on the fuel dribble process. High-speed X-ray phase-contrast images obtained at room temperature conditions (297 K) at the Advanced Photon Source at Argonne National Laboratory, together with diffused back-illumination images captured at a wide range of temperature conditions (293-900 K) by CMT Motores Termicos were analysed and compared quantitatively. We found a good agreement between image sets obtained by Argonne National Laboratory and CMT Motores Termicos using different imaging techniques. The maximum dribble volume within the field of view of the imaging system and the mean rate of fuel dribble were considered as characteristic parameters of the fuel dribble process. Analysis showed that the absolute mean dribble rate increases with temperature when injection pressure is higher than 1000 bar and slightly decreases at high injection pressures (>500 bar) when temperature is close to 293 K. Larger maximum volumes of the fuel dribble were observed at lower gas temperatures (similar to 473 K) and low gas pressures (<30 bar), with a slight dependence on injection pressure.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The image processing research was supported by the United Kingdom's Engineering and Physical Science Research Council (Grants EP/K020528/1 and EP/M009424/1) and BP Formulated Products Technology. The X-ray measurements were performed at the Advanced Photon Source at Argonne National Laboratory. Use of the Advanced Photon Source (APS) is supported by the U.S. Department of Energy (DOE) under Contract No. DEAC02-06CH11357. The X-ray component of this research was partially funded by DOE's Vehicle Technologies Program, Office of Energy Efficiency and Renewable Energy.Sechenyh, V.; Duke, DJ.; Swantek, AB.; Matusik, KE.; Kastengren, AL.; Powell, CF.; Viera, A.... (2020). Quantitative analysis of dribble volumes and rates using three-dimensional reconstruction of X-ray and diffused back-illumination images of diesel sprays. International Journal of Engine Research. 21(1):43-54. https://doi.org/10.1177/1468087419860955S4354211Örley, F., Hickel, S., Schmidt, S. J., & Adams, N. A. (2016). Large-Eddy Simulation of turbulent, cavitating fuel flow inside a 9-hole Diesel injector including needle movement. International Journal of Engine Research, 18(3), 195-211. doi:10.1177/1468087416643901Benajes, J., Novella, R., De Lima, D., & Tribotté, P. (2014). Analysis of combustion concepts in a newly designed two-stroke high-speed direct injection compression ignition engine. International Journal of Engine Research, 16(1), 52-67. doi:10.1177/1468087414562867Moon, S., Huang, W., Li, Z., & Wang, J. (2016). End-of-injection fuel dribble of multi-hole diesel injector: Comprehensive investigation of phenomenon and discussion on control strategy. Applied Energy, 179, 7-16. doi:10.1016/j.apenergy.2016.06.116Kook, S., Pickett, L. M., & Musculus, M. P. B. (2009). Influence of Diesel Injection Parameters on End-of-Injection Liquid Length Recession. SAE International Journal of Engines, 2(1), 1194-1210. doi:10.4271/2009-01-1356Kastengren, A., Powell, C. F., Tilocco, F. Z., Liu, Z., Moon, S., Zhang, X., & Gao, J. (2012). End-of-Injection Behavior of Diesel Sprays Measured With X-Ray Radiography. Journal of Engineering for Gas Turbines and Power, 134(9). doi:10.1115/1.4006981Manin, J., Bardi, M., Pickett, L. M., & Payri, R. (2016). Boundary condition and fuel composition effects on injection processes of high-pressure sprays at the microscopic level. International Journal of Multiphase Flow, 83, 267-278. doi:10.1016/j.ijmultiphaseflow.2015.12.001Payri, R., Bracho, G., Marti-Aldaravi, P., & Viera, A. (2017). NEAR FIELD VISUALIZATION OF DIESEL SPRAY FOR DIFFERENT NOZZLE INCLINATION ANGLES IN NON-VAPORIZING CONDITIONS. Atomization and Sprays, 27(3), 251-267. doi:10.1615/atomizspr.2017017949Gimeno, J., Martí-Aldaraví, P., Carreres, M., & Peraza, J. E. (2018). Effect of the nozzle holder on injected fuel temperature for experimental test rigs and its influence on diesel sprays. International Journal of Engine Research, 19(3), 374-389. doi:10.1177/1468087417751531Payri, R., Salvador, F. J., Manin, J., & Viera, A. (2016). Diesel ignition delay and lift-off length through different methodologies using a multi-hole injector. Applied Energy, 162, 541-550. doi:10.1016/j.apenergy.2015.10.118Duke, D. J., Matusik, K. E., Kastengren, A. L., Swantek, A. B., Sovis, N., Payri, R., … Powell, C. F. (2017). X-ray radiography of cavitation in a beryllium alloy nozzle. International Journal of Engine Research, 18(1-2), 39-50. doi:10.1177/1468087416685965Duke, D., Swantek, A., Kastengren, A., Fezzaa, K., & Powell, C. (2015). Recent Developments in X-ray Diagnostics for Cavitation. SAE International Journal of Fuels and Lubricants, 8(1), 135-146. doi:10.4271/2015-01-0918Walko, D. A., Adams, B. W., Doumy, G., Dufresne, E. M., Li, Y., March, A. M., … Zhu, Y. (2016). Developments in time-resolved x-ray research at APS beamline 7ID. doi:10.1063/1.4952871Fessler, J. A., & Macovski, A. (1991). Object-based 3-D reconstruction of arterial trees from magnetic resonance angiograms. IEEE Transactions on Medical Imaging, 10(1), 25-39. doi:10.1109/42.75608Canny, J. (1986). A Computational Approach to Edge Detection. IEEE Transactions on Pattern Analysis and Machine Intelligence, PAMI-8(6), 679-698. doi:10.1109/tpami.1986.4767851Kastengren, A. L., Tilocco, F. Z., Duke, D. J., Powell, C. F., Zhang, X., & Moon, S. (2014). TIME-RESOLVED X-RAY RADIOGRAPHY OF SPRAYS FROM ENGINE COMBUSTION NETWORK SPRAY A DIESEL INJECTORS. Atomization and Sprays, 24(3), 251-272. doi:10.1615/atomizspr.2013008642Edelsbrunner, H., & Mücke, E. P. (1994). Three-dimensional alpha shapes. ACM Transactions on Graphics, 13(1), 43-72. doi:10.1145/174462.156635Lafarge, T., Pateiro-López, B., Possolo, A., & Dunkers, J. P. (2014). RImplementation of a Polyhedral Approximation to a 3D Set of Points Using theα-Shape. Journal of Statistical Software, 56(4). doi:10.18637/jss.v056.i04Koci, C., Dempsey, A., Nudd, J., & Knier, B. (2017). Understanding Hydrocarbon Emissions in Heavy Duty Diesel Engines Combining Experimental and Computational Methods. SAE International Journal of Engines, 10(3), 1093-1109. doi:10.4271/2017-01-070

Autism as a disorder of neural information processing: directions for research and targets for therapy

The broad variation in phenotypes and severities within autism spectrum disorders suggests the involvement of multiple predisposing factors, interacting in complex ways with normal developmental courses and gradients. Identification of these factors, and the common developmental path into which theyfeed, is hampered bythe large degrees of convergence from causal factors to altered brain development, and divergence from abnormal brain development into altered cognition and behaviour. Genetic, neurochemical, neuroimaging and behavioural findings on autism, as well as studies of normal development and of genetic syndromes that share symptoms with autism, offer hypotheses as to the nature of causal factors and their possible effects on the structure and dynamics of neural systems. Such alterations in neural properties may in turn perturb activity-dependent development, giving rise to a complex behavioural syndrome many steps removed from the root causes. Animal models based on genetic, neurochemical, neurophysiological, and behavioural manipulations offer the possibility of exploring these developmental processes in detail, as do human studies addressing endophenotypes beyond the diagnosis itself

Geographical Affinities of the HapMap Samples

The HapMap samples were collected for medical-genetic studies, but are also widely used in population-genetic and evolutionary investigations. Yet the ascertainment of the samples differs from most population-genetic studies which collect individuals who live in the same local region as their ancestors. What effects could this non-standard ascertainment have on the interpretation of HapMap results?We compared the HapMap samples with more conventionally-ascertained samples used in population- and forensic-genetic studies, including the HGDP-CEPH panel, making use of published genome-wide autosomal SNP data and Y-STR haplotypes, as well as producing new Y-STR data. We found that the HapMap samples were representative of their broad geographical regions of ancestry according to all tests applied. The YRI and JPT were indistinguishable from independent samples of Yoruba and Japanese in all ways investigated. However, both the CHB and the CEU were distinguishable from all other HGDP-CEPH populations with autosomal markers, and both showed Y-STR similarities to unusually large numbers of populations, perhaps reflecting their admixed origins.The CHB and JPT are readily distinguished from one another with both autosomal and Y-chromosomal markers, and results obtained after combining them into a single sample should be interpreted with caution. The CEU are better described as being of Western European ancestry than of Northern European ancestry as often reported. Both the CHB and CEU show subtle but detectable signs of admixture. Thus the YRI and JPT samples are well-suited to standard population-genetic studies, but the CHB and CEU less so

Kinetics of biodegradation of diethylketone by Arthrobacter viscosus

The performance of an Arthrobacter viscosus culture to remove diethylketone from aqueous solutions was evaluated. The effect of initial concentration of diethylketone on the growth of the bacteria was evaluated for the range of concentration between 0 and 4.8 g/l, aiming to evaluate a possible toxicological effect. The maximum specific growth rate achieved is 0.221 h-1 at 1.6 g/l of initial diethylketone concentration, suggesting that for higher concentrations an inhibitory effect on the growth occurs. The removal percentages obtained were approximately 88%, for all the initial concentrations tested. The kinetic parameters were estimated using four growth kinetic models for biodegradation of organic compounds available in the literature. The experimental data found is well fitted by the Haldane model (R2 = 1) as compared to Monod model (R2 = 0.99), Powell (R2 = 0.82) and Loung model (R2 = 0.95). The biodegradation of diethylketone using concentrated biomass was studied for an initial diethylketone concentration ranging from 0.8–3.9 g/l in a batch with recirculation mode of operation. The biodegradation rate found followed the pseudo-second order kinetics and the resulting kinetic parameters are reported. The removal percentages obtained were approximately 100%, for all the initial concentrations tested, suggesting that the increment on the biomass concentration allows better results in terms of removal of diethylketone. This study showed that these bacteria are very effective for the removal of diethylketone from aqueous solutions.The authors would like to gratefully acknowledge the financial support of this project by the Fundacao para a Ciencia e Tecnologia (FCT), Ministerio da Ciencia e Tecnologia, Portugal and Fundo Social Europeu (FSE). Cristina Quintelas thanks FCT for a Post-Doc grant

Growth hormone axis in chronic kidney disease

Chronic kidney disease (CKD) in children is associated with dramatic changes in the growth hormone (GH) and insulin-like growth factor (IGF-1) axis, resulting in growth retardation. Moderate-to-severe growth retardation in CKD is associated with increased morbidity and mortality. Renal failure is a state of GH resistance and not GH deficiency. Some mechanisms of GH resistance are: reduced density of GH receptors in target organs, impaired GH-activated post-receptor Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and reduced levels of free IGF-1 due to increased inhibitory IGF-binding proteins (IGFBPs). Treatment with recombinant human growth hormone (rhGH) has been proven to be safe and efficacious in children with CKD. Even though rhGH has been shown to improve catch-up growth and to allow the child to achieve normal adult height, the final adult height is still significantly below the genetic target. Growth retardation may persist after renal transplantation due to multiple factors, such as steroid use, decreased renal function and an abnormal GH–IGF1 axis. Those below age 6 years are the ones to benefit most from transplantation in demonstrating acceleration in linear growth. Newer treatment modalities targeting the GH resistance with recombinant human IGF-1 (rhIGF-1), recombinant human IGFBP3 (rhIGFBP3) and IGFBP displacers are under investigation and may prove to be more effective in treating growth failure in CKD

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

The antimicrobial effects of the alginate oligomer OligoG CF-5/20 are independent of direct bacterial cell membrane disruption

Concerns about acquisition of antibiotic resistance have led to increasing demand for new antimicrobial therapies. OligoG CF-5/20 is an alginate oligosaccharide previously shown to have antimicrobial and antibiotic potentiating activity. We investigated the structural modification of the bacterial cell wall by OligoG CF-5/20 and its effect on membrane permeability. Binding of OligoG CF-5/20 to the bacterial cell surface was demonstrated in Gram-negative bacteria. Permeability assays revealed that OligoG CF-5/20 had virtually no membrane-perturbing effects. Lipopolysaccharide (LPS) surface charge and aggregation were unaltered in the presence of OligoG CF-5/20. Small angle neutron scattering and circular dichroism spectroscopy showed no substantial change to the structure of LPS in the presence of OligoG CF-5/20, however, isothermal titration calorimetry demonstrated a weak calcium-mediated interaction. Metabolomic analysis confirmed no change in cellular metabolic response to a range of osmolytes when treated with OligoG CF-5/20. This data shows that, although weak interactions occur between LPS and OligoG CF-5/20 in the presence of calcium, the antimicrobial effects of OligoG CF-5/20 are not related to the induction of structural alterations in the LPS or cell permeability. These results suggest a novel mechanism of action that may avoid the common route in acquisition of resistance via LPS structural modification

Self Assembly and Properties of C:WO3 Nano-Platelets and C:VO2/V2O5 Triangular Capsules Produced by Laser Solution Photolysis

Laser photolysis of WCl6 in ethanol and a specific mixture of V2O5 and VCl3 in ethanol lead to carbon modified vanadium and tungsten oxides with interesting properties. The presence of graphene’s aromatic rings (from the vibrational frequency of 1,600 cm−1) together with C–C bonding of carbon (from the Raman shift of 1,124 cm−1) present unique optical, vibrational, electronic and structural properties of the intended tungsten trioxide and vanadium dioxide materials. The morphology of these samples shows nano-platelets in WOx samples and, in VOx samples, encapsulated spherical quantum dots in conjunction with fullerenes of VOx. Conductivity studies revealed that the VO2/V2O5 nanostructures are more sensitive to Cl than to the presence of ethanol, whereas the C:WO3 nano-platelets are more sensitive to ethanol than atomic C