370 research outputs found

    Earth rotation and core topography

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    The NASA Geodynamics program has as one of its missions highly accurate monitoring of polar motion, including changes in length of day (LOD). These observations place fundamental constraints on processes occurring in the atmosphere, in the mantle, and in the core of the planet. Short-timescale (t less than or approx 1 yr) variations in LOD are mainly the result of interaction between the atmosphere and the solid earth, while variations in LOD on decade timescales result from the exchange of angular momentum between the mantle and the fluid core. One mechanism for this exchange of angular momentum is through topographic coupling between pressure variations associated with flow in the core interacting with topography at the core-mantel boundary (CMB). Work done under another NASA grant addressing the origin of long-wavelength geoid anomalies as well as evidence from seismology, resulted in several models of CMB topography. The purpose of work supported by NAG5-819 was to study further the problem of CMB topography, using geodesy, fluid mechanics, geomagnetics, and seismology. This is a final report

    Evolution and diversity of the courtship repertoire in the Drosophila montium species group (Diptera: Drosophilidae)

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    SYW is funded by the National Scientific Foundation of China (31372187). MGR is funded by the NERC, UK (grants NE/E015255/1 and NE/J020818/1).Changes in elements of courtship behaviour can influence sexual isolation between species. Large‐scale analyses of changes, including loss and gain of courtship elements, across a relatively complete phylogenetic group are rare but needed to understand the significance of such changes, for example whether the gain and loss of courtship elements are essentially arbitrary or equally reversible. In most species of Drosophila, courtship, including singing, mainly occurs before mounting as pre‐mounting courtship. The Drosophila montium species group is unusual because loss of pre‐mounting courtship and gain of post‐mounting one has been detected in this group. Here we provide an extensive analysis on the courtship repertoire and songs of 42 species in this group. Synchronously captured video and audio recordings were analysed to describe courtship patterns and male courtship songs and changes were analysed in a phylogenetic context. Ancestral state reconstruction suggests that a gain of post‐mounting courtship singing at the ancestor of this species group has been accompanied with a concurrent decrease in the incidence of pre‐mounting courtship singing and has led to subsequent further decrease and eventually complete loss of pre‐mounting courtship song in several lineages. Alongside this evolutionary trend towards post‐mounting courtship, sine song and a special type of “high pulse repetition song” have become more widely used for courtship during species diversification in the montium group. It is likely that the elaboration of post‐mounting courtship behaviours is associated with changes in the relative importance of pre‐ and post‐mounting components of mating systems, such as sperm competition or cryptic female choice.PostprintPeer reviewe

    NMDAR1 autoantibodies amplify behavioral phenotypes of genetic white matter inflammation: a mild encephalitis model with neuropsychiatric relevance

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    Encephalitis has an estimated prevalence of ≤0.01%. Even with extensive diagnostic work-up, an infectious etiology is identified or suspected in <50% of cases, suggesting a role for etiologically unclear, noninfectious processes. Mild encephalitis runs frequently unnoticed, despite slight neuroinflammation detectable postmortem in many neuropsychiatric illnesses. A widely unexplored field in humans, though clearly documented in rodents, is genetic brain inflammation, particularly that associated with myelin abnormalities, inducing primary white matter encephalitis. We hypothesized that “autoimmune encephalitides” may result from any brain inflammation concurring with the presence of brain antigen-directed autoantibodies, e.g., against N-methyl-D-aspartate-receptor NR1 (NMDAR1-AB), which are not causal of, but may considerably shape the encephalitis phenotype. We therefore immunized young female Cnp−/− mice lacking the structural myelin protein 2′-3′-cyclic nucleotide 3′-phosphodiesterase (Cnp) with a “cocktail” of NMDAR1 peptides. Cnp−/− mice exhibit early low-grade inflammation of white matter tracts and blood–brain barrier disruption. Our novel mental-time-travel test disclosed that Cnp−/− mice are compromised in what–where–when orientation, but this episodic memory readout was not further deteriorated by NMDAR1-AB. In contrast, comparing wild-type and Cnp−/− mice without/with NMDAR1-AB regarding hippocampal learning/memory and motor balance/coordination revealed distinct stair patterns of behavioral pathology. To elucidate a potential contribution of oligodendroglial NMDAR downregulation to NMDAR1-AB effects, we generated conditional NR1 knockout mice. These mice displayed normal Morris water maze and mental-time-travel, but beam balance performance was similar to immunized Cnp−/−. Immunohistochemistry confirmed neuroinflammation/neurodegeneration in Cnp−/− mice, yet without add-on effect of NMDAR1-AB. To conclude, genetic brain inflammation may explain an encephalitic component underlying autoimmune conditions

    Topographic Core-Mantle Coupling and Fluctuations in the Earth's Rotation

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    Astronomically-determined irregular fluctuations in the Earth's rotation vector on decadal time scales can be used to estimate the fluctuating torque on the lower surface of the Earth's mantle produced by magnetohydrodynamic flow in the underlying liquid metallic core. A method has been proposed for testing the hypothesis that the torque is due primarily to fluctuating dynamic pressure forces acting on irregular topographic features of the core-mantle boundary and also on the equatorial bulge. The method exploits (a) geostrophically-constrained models of fluid motions in the upper reaches of the core based on geomagnetic secular variation data, and (b) patterns of the topography of the CMB based on the mantle flow models constrained by data from seismic tomography, determinations of long wave-length anomalies of the Earth's gravitational field and other geophysical and geodetic data. According to the present study, the magnitude of the axial component of the torque implied by determinations of irregular changes in the length of the day is compatible with models of the Earth's deep interior characterized by the presence of irregular CMB topography of effective “height” no more than about 0.5 km (about 6% of the equatorial bulge) and strong horizontal variations in the properties of the D″ layer at the base of the mantle. The investigation is now being extended to cover a wider range of epochs and also the case of polar motion on decadal time scales produced by fluctuations in the equatorial components of the torque

    Non-perturbative dynamics of hot non-Abelian gauge fields: beyond leading log approximation

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    Many aspects of high-temperature gauge theories, such as the electroweak baryon number violation rate, color conductivity, and the hard gluon damping rate, have previously been understood only at leading logarithmic order (that is, neglecting effects suppressed only by an inverse logarithm of the gauge coupling). We discuss how to systematically go beyond leading logarithmic order in the analysis of physical quantities. Specifically, we extend to next-to-leading-log order (NLLO) the simple leading-log effective theory due to Bodeker that describes non-perturbative color physics in hot non-Abelian plasmas. A suitable scaling analysis is used to show that no new operators enter the effective theory at next-to-leading-log order. However, a NLLO calculation of the color conductivity is required, and we report the resulting value. Our NLLO result for the color conductivity can be trivially combined with previous numerical work by G. Moore to yield a NLLO result for the hot electroweak baryon number violation rate.Comment: 20 pages, 1 figur

    Annotation of two large contiguous regions from the Haemonchus contortus genome using RNA-seq and comparative analysis with Caenorhabditis elegans

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    The genomes of numerous parasitic nematodes are currently being sequenced, but their complexity and size, together with high levels of intra-specific sequence variation and a lack of reference genomes, makes their assembly and annotation a challenging task. Haemonchus contortus is an economically significant parasite of livestock that is widely used for basic research as well as for vaccine development and drug discovery. It is one of many medically and economically important parasites within the strongylid nematode group. This group of parasites has the closest phylogenetic relationship with the model organism Caenorhabditis elegans, making comparative analysis a potentially powerful tool for genome annotation and functional studies. To investigate this hypothesis, we sequenced two contiguous fragments from the H. contortus genome and undertook detailed annotation and comparative analysis with C. elegans. The adult H. contortus transcriptome was sequenced using an Illumina platform and RNA-seq was used to annotate a 409 kb overlapping BAC tiling path relating to the X chromosome and a 181 kb BAC insert relating to chromosome I. In total, 40 genes and 12 putative transposable elements were identified. 97.5% of the annotated genes had detectable homologues in C. elegans of which 60% had putative orthologues, significantly higher than previous analyses based on EST analysis. Gene density appears to be less in H. contortus than in C. elegans, with annotated H. contortus genes being an average of two-to-three times larger than their putative C. elegans orthologues due to a greater intron number and size. Synteny appears high but gene order is generally poorly conserved, although areas of conserved microsynteny are apparent. C. elegans operons appear to be partially conserved in H. contortus. Our findings suggest that a combination of RNA-seq and comparative analysis with C. elegans is a powerful approach for the annotation and analysis of strongylid nematode genomes

    MGMT gene promoter methylation correlates with tolerance of temozolomide treatment in melanoma but not with clinical outcome

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    BACKGROUND: Despite limited clinical efficacy, treatment with dacarbazine or temozolomide (TMZ) remains the standard therapy for metastatic melanoma. In glioblastoma, promoter methylation of the counteracting DNA repair enzyme O(6)-methylguanine-DNA-methyltransferase (MGMT) correlates with survival of patients exposed to TMZ in combination with radiotherapy. For melanoma, data are limited and controversial. METHODS: Biopsy samples from 122 patients with metastatic melanoma being treated with TMZ in two multicenter studies of the Dermatologic Cooperative Oncology Group were investigated for MGMT promoter methylation. We used the COBRA (combined bisulphite restriction analysis) technique to determine aberrant methylation of CpG islands in small amounts of genomic DNA isolated from paraffin-embedded tissue sections. To detect aberrant methylation, bisulphite-treated DNA was amplified by PCR, enzyme restricted, and visualised by gel electrophoresis. RESULTS: Correlation with clinical data from 117 evaluable patients in a best-response evaluation indicated no statistically significant association between MGMT promoter methylation status and response. A methylated MGMT promoter was observed in 34.8% of responders and 23.4% of non-responders (P=0.29). In addition, no survival advantage for patients with a methylated MGMT promoter was detectable (P=0.79). Interestingly, we found a significant correlation between MGMT methylation and tolerance of therapy. Patients with a methylated MGMT promoter had more severe adverse events, requiring more TMZ dose reductions or discontinuations (P=0.007; OR 2.7 (95% CI: 1.32-5.7)). Analysis of MGMT promoter methylation comparing primaries and different metastases over the clinical course revealed no statistical difference (P=0.49). CONCLUSIONS: In advanced melanoma MGMT promoter, methylation correlates with tolerance of therapy, but not with clinical outcome
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