Autumn MIST 2017

Jasmine Sandhu, Georgina Graham, Sarah Bentley and John Coxon report on the annual Magnetosphere, Ionosphere, and Solar–Terrestrial (MIST) meeting, highlighting science results from the Cassini and Juno missions

Variability of Quasilinear Diffusion Coefficients for Plasmaspheric Hiss

In the outer radiation belt, the acceleration and loss of high‐energy electrons is largely controlled by wave‐particle interactions. Quasilinear diffusion coefficients are an efficient way to capture the small‐scale physics of wave‐particle interactions due to magnetospheric wave modes such as plasmaspheric hiss. The strength of quasilinear diffusion coefficients as a function of energy and pitch angle depends on both wave parameters and plasma parameters such as ambient magnetic field strength, plasma number density, and composition. For plasmaspheric hiss in the magnetosphere, observations indicate large variations in the wave intensity and wave normal angle, but less is known about the simultaneous variability of the magnetic field and number density. We use in situ measurements from the Van Allen Probe mission to demonstrate the variability of selected factors that control the size and shape of pitch angle diffusion coefficients: wave intensity, magnetic field strength, and electron number density. We then compare with the variability of diffusion coefficients calculated individually from colocated and simultaneous groups of measurements. We show that the distribution of the plasmaspheric hiss diffusion coefficients is highly non‐Gaussian with large variance and that the distributions themselves vary strongly across the three phase space bins studied. In most bins studied, the plasmaspheric hiss diffusion coefficients tend to increase with geomagnetic activity, but our results indicate that new approaches that include natural variability may yield improved parameterizations. We suggest methods like stochastic parameterization of wave‐particle interactions could use variability information to improve modeling of the outer radiation belt

Temporal variability of quasi-linear pitch-angle diffusion

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData availability statement; The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://emfisis.physics.uiowa.edu/data/index; https://doi.org/10.17864/1947.212, Ensemble experiment data can be found at https://doi.org/10.25398/rd.northumbria.2126623.Kinetic wave-particle interactions in Earth’s outer radiation belt energize and scatter high-energy electrons, playing an important role in the dynamic variation of the extent and intensity of the outer belt. It is possible to model the effects of wave-particle interactions across long length and time scales using quasi-linear theory, leading to a Fokker-Planck equation to describe the effects of the waves on the high energy electrons. This powerful theory renders the efficacy of the wave-particle interaction in a diffusion coefficient that varies with energy or momentum and pitch angle. In this article we determine how the Fokker-Planck equation responds to the temporal variation of the quasi-linear diffusion coefficient in the case of pitch-angle diffusion due to plasmaspheric hiss. Guided by in-situ observations of how hiss wave activity and local number density change in time, we use stochastic parameterisation to describe the temporal evolution of hiss diffusion coefficients in ensemble numerical experiments. These experiments are informed by observations from three different example locations in near-Earth space, and a comparison of the results indicates that local differences in the distribution of diffusion coefficients can result in material differences to the ensemble solutions. We demonstrate that ensemble solutions of the Fokker-Planck equation depend both upon the timescale of variability (varied between minutes and hours), and the shape of the distribution of diffusion coefficients. Based upon theoretical construction of the diffusion coefficients and the results presented here, we argue that there is a useful maximum averaging timescale that should be used to construct a diffusion coefficient from observations, and that this timescale is likely less than the orbital period of most inner magnetospheric missions. We discuss time and length scales of wave-particle interactions relative to the drift velocity of high-energy electrons and confirm that arithmetic drift-averaging is can be appropriate in some cases. We show that in some locations, rare but large values of the diffusion coefficient occur during periods of relatively low number density. Ensemble solutions are sensitive to the presence of these rare values, supporting the need for accurate cold plasma density models in radiation belt descriptions.Natural Environment Research Council (NERC)Science and Technology Facilities Council (STFC)University of ExeterAlexander von Humboldt Postdoctoral Research Fellowshi

Validity of sports watches when estimating energy expenditure during running

The aim of this study was to assess the accuracy of three different sport watches in estimating energy expenditure during aerobic and anaerobic running

Association between DNA Damage Response and Repair Genes and Risk of Invasive Serous Ovarian Cancer

BACKGROUND: We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study (NCOCS), a population-based, case-control study. METHODS/PRINCIPAL FINDINGS: The analysis was restricted to 364 invasive serous ovarian cancer cases and 761 controls of white, non-Hispanic race. Statistical analysis was two staged: a screen using marginal Bayes factors (BFs) for 484 SNPs and a modeling stage in which we calculated multivariate adjusted posterior probabilities of association for 77 SNPs that passed the screen. These probabilities were conditional on subject age at diagnosis/interview, batch, a DNA quality metric and genotypes of other SNPs and allowed for uncertainty in the genetic parameterizations of the SNPs and number of associated SNPs. Six SNPs had Bayes factors greater than 10 in favor of an association with invasive serous ovarian cancer. These included rs5762746 (median OR(odds ratio)(per allele) = 0.66; 95% credible interval (CI) = 0.44-1.00) and rs6005835 (median OR(per allele) = 0.69; 95% CI = 0.53-0.91) in CHEK2, rs2078486 (median OR(per allele) = 1.65; 95% CI = 1.21-2.25) and rs12951053 (median OR(per allele) = 1.65; 95% CI = 1.20-2.26) in TP53, rs411697 (median OR (rare homozygote) = 0.53; 95% CI = 0.35 - 0.79) in BACH1 and rs10131 (median OR( rare homozygote) = not estimable) in LIG4. The six most highly associated SNPs are either predicted to be functionally significant or are in LD with such a variant. The variants in TP53 were confirmed to be associated in a large follow-up study. CONCLUSIONS/SIGNIFICANCE: Based on our findings, further follow-up of the DNA repair and response pathways in a larger dataset is warranted to confirm these results

Identification of Intracellular and Plasma Membrane Calcium Channel Homologues in Pathogenic Parasites

Ca2+ channels regulate many crucial processes within cells and their abnormal activity can be damaging to cell survival, suggesting that they might represent attractive therapeutic targets in pathogenic organisms. Parasitic diseases such as malaria, leishmaniasis, trypanosomiasis and schistosomiasis are responsible for millions of deaths each year worldwide. The genomes of many pathogenic parasites have recently been sequenced, opening the way for rational design of targeted therapies. We analyzed genomes of pathogenic protozoan parasites as well as the genome of Schistosoma mansoni, and show the existence within them of genes encoding homologues of mammalian intracellular Ca2+ release channels: inositol 1,4,5-trisphosphate receptors (IP3Rs), ryanodine receptors (RyRs), two-pore Ca2+ channels (TPCs) and intracellular transient receptor potential (Trp) channels. The genomes of Trypanosoma, Leishmania and S. mansoni parasites encode IP3R/RyR and Trp channel homologues, and that of S. mansoni additionally encodes a TPC homologue. In contrast, apicomplexan parasites lack genes encoding IP3R/RyR homologues and possess only genes encoding TPC and Trp channel homologues (Toxoplasma gondii) or Trp channel homologues alone. The genomes of parasites also encode homologues of mammalian Ca2+ influx channels, including voltage-gated Ca2+ channels and plasma membrane Trp channels. The genome of S. mansoni also encodes Orai Ca2+ channel and STIM Ca2+ sensor homologues, suggesting that store-operated Ca2+ entry may occur in this parasite. Many anti-parasitic agents alter parasite Ca2+ homeostasis and some are known modulators of mammalian Ca2+ channels, suggesting that parasite Ca2+ channel homologues might be the targets of some current anti-parasitic drugs. Differences between human and parasite Ca2+ channels suggest that pathogen-specific targeting of these channels may be an attractive therapeutic prospect

In Silico Prediction and Analysis of Caenorhabditis EF-hand Containing Proteins

Calcium (Ca+2) is a ubiquitous messenger in eukaryotes including Caenorhabditis. Ca+2-mediated signalling processes are usually carried out through well characterized proteins like calmodulin (CaM) and other Ca+2 binding proteins (CaBP). These proteins interact with different targets and activate it by bringing conformational changes. Majority of the EF-hand proteins in Caenorhabditis contain Ca+2 binding motifs. Here, we have performed homology modelling of CaM-like proteins using the crystal structure of Drosophila melanogaster CaM as a template. Molecular docking was applied to explore the binding mechanism of CaM-like proteins and IQ1 motif which is a ∼25 residues and conform to the consensus sequence (I, L, V)QXXXRXXXX(R,K) to serve as a binding site for different EF hand proteins. We made an attempt to identify all the EF-hand (a helix-loop-helix structure characterized by a 12 residues loop sequence involved in metal coordination) containing proteins and their Ca+2 binding affinity in Caenorhabditis by analysing the complete genome sequence. Docking studies revealed that F165, F169, L29, E33, F44, L57, M61, M96, M97, M108, G65, V115, F93, N104, E144 of CaM-like protein is involved in the interaction with IQ1 motif. A maximum of 170 EF-hand proteins and 39 non-EF-hand proteins with Ca+2/metal binding motif were identified. Diverse proteins including enzyme, transcription, translation and large number of unknown proteins have one or more putative EF-hands. Phylogenetic analysis revealed seven major classes/groups that contain some families of proteins. Various domains that we identified in the EF-hand proteins (uncharacterized) would help in elucidating their functions. It is the first report of its kind where calcium binding loop sequences of EF-hand proteins were analyzed to decipher their calcium affinities. Variation in Ca+2-binding affinity of EF-hand CaBP could be further used to study the behaviour of these proteins. Our analyses postulated that Ca+2 is likely to be key player in Caenorhabditis cell signalling

A point mutation in cpsE renders Streptococcus pneumoniae nonencapsulated and enhances its growth, adherence and competence.

BACKGROUND: The polysaccharide capsule is a major virulence factor of the important human pathogen Streptococcus pneumoniae. However, S. pneumoniae strains lacking capsule do occur. RESULTS: Here, we report a nasopharyngeal isolate of Streptococcus pneumoniae composed of a mixture of two phenotypes; one encapsulated (serotype 18C) and the other nonencapsulated, determined by serotyping, electron microscopy and fluorescence isothiocyanate dextran exclusion assay.By whole genome sequencing, we demonstrated that the phenotypes differ by a single nucleotide base pair in capsular gene cpsE (C to G change at gene position 1135) predicted to result in amino acid change from arginine to glycine at position 379, located in the cytoplasmic, enzymatically active, region of this transmembrane protein. This SNP is responsible for loss of capsule production as the phenotype is transferred with the capsule operon. The nonencapsulated variant is superior in growth in vitro and is also 117-fold more adherent to and more invasive into Detroit 562 human epithelial cells than the encapsulated variant.Expression of six competence pathway genes and one competence-associated gene was 11 to 34-fold higher in the nonencapsulated variant than the encapsulated and transformation frequency was 3.7-fold greater. CONCLUSIONS: We identified a new single point mutation in capsule gene cpsE of a clinical S. pneumoniae serotype 18C isolate sufficient to cause loss of capsule expression resulting in the co-existence of the encapsulated and nonencapsulated phenotype. The mutation caused phenotypic changes in growth, adherence to epithelial cells and transformability. Mutation in capsule gene cpsE may be a way for S. pneumoniae to lose its capsule and increase its colonization potential

Optimization of interneuron function by direct coupling of cell migration and axonal targeting

Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb—a gene that is preferentially expressed by these cells—cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex