Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine.

Demonstration of survival and outcome of progressive multifocal leukoencephalopathy (PML) in a 56-year-old patient with common variable immunodeficiency, consisting of severe hypogammaglobulinemia and CD4+ T lymphocytopenia, during continuous treatment with mirtazapine (30 mg/day) and mefloquine (250 mg/week) over 23 months. Regular clinical examinations including Rankin scale and Barthel index, nine-hole peg and box and block tests, Berg balance, 10-m walking tests, and Montreal Cognitive Assessment (MoCA) were done. Laboratory diagnostics included complete blood count and JC virus (JCV) concentration in cerebrospinal fluid (CSF). The noncoding control region (NCCR) of JCV, important for neurotropism and neurovirulence, was sequenced. Repetitive MRI investigated the course of brain lesions. JCV was detected in increasing concentrations (peak 2568 copies/ml CSF), and its NCCR was genetically rearranged. Under treatment, the rearrangement changed toward the archetype sequence, and later JCV DNA became undetectable. Total brain lesion volume decreased (8.54 to 3.97 cm(3)) and atrophy increased. Barthel (60 to 100 to 80 points) and Rankin (4 to 2 to 3) scores, gait stability, and box and block (7, 35, 25 pieces) and nine-hole peg (300, 50, 300 s) test performances first improved but subsequently worsened. Cognition and walking speed remained stable. Despite initial rapid deterioration, the patient survived under continuous treatment with mirtazapine and mefloquine even though he belongs to a PML subgroup that is usually fatal within a few months. This course was paralleled by JCV clones with presumably lower replication capability before JCV became undetectable. Neurological deficits were due to PML lesions and progressive brain atrophy.

Time variable Earth’s gravity field from SLR satellites

The time variable Earth’s gravity field contains information about the mass transport within the system Earth, i.e., the relationship between mass variations in the atmosphere, oceans, land hydrology, and ice sheets. For many years, satellite laser ranging (SLR) observations to geodetic satellites have provided valuable information of the low-degree coefficients of the Earth’s gravity field. Today, the Gravity Recovery and Climate Experiment (GRACE) mission is the major source of information for the time variable field of a high spatial resolution. We recover the low-degree coefficients of the time variable Earth’s gravity field using SLR observations up to nine geodetic satellites: LAGEOS-1, LAGEOS-2, Starlette, Stella, AJISAI, LARES, Larets, BLITS, and Beacon-C. We estimate monthly gravity field coefficients up to degree and order 10/10 for the time span 2003–2013 and we compare the results with the GRACE-derived gravity field coefficients. We show that not only degree-2 gravity field coefficients can be well determined from SLR, but also other coefficients up to degree 10 using the combination of short 1-day arcs for low orbiting satellites and 10-day arcs for LAGEOS-1/2. In this way, LAGEOS-1/2 allow recovering zonal terms, which are associated with long-term satellite orbit perturbations, whereas the tesseral and sectorial terms benefit most from low orbiting satellites, whose orbit modeling deficiencies are minimized due to short 1-day arcs. The amplitudes of the annual signal in the low-degree gravity field coefficients derived from SLR agree with GRACE K-band results at a level of 77 %. This implies that SLR has a great potential to fill the gap between the current GRACE and the future GRACE Follow-On mission for recovering of the seasonal variations and secular trends of the longest wavelengths in gravity field, which are associated with the large-scale mass transport in the system Earth.

Time Variable Gravity: Contributions of GOCE Satellite Data to Monthly and Bi-monthly GRACE Gravity Estimates

A feasibility study by Pail et al. (Can GOCE help to improve temporal gravity field estimates? In: Ouwehand L (ed) Proceedings of the 4th International GOCE User Workshop, ESA Publication SP-696, 2011b) shows that GOCE (‘Gravity field and steady-state Ocean Circulation Explorer’) satellite gravity gradiometer (SGG) data in combination with GPS derived orbit data (satellite-to-satellite tracking: SST-hl) can be used to stabilize and reduce the striping pattern of a bi-monthly GRACE (‘Gravity Recovery and Climate Experiment’) gravity field estimate. In this study several monthly (and bi-monthly) combinations of GRACE with GOCE SGG and GOCE SST-hl data on the basis of normal equations are investigated. Our aim is to assess the role of the gradients (solely) in the combination and whether already one month of GOCE observations provides sufficient data for having an impact in the combination. The estimation of clean and stable monthly GOCE SGG normal equations at high resolution ( >  d/o 150) is found to be difficult, and the SGG component, solely, does not show significant added value to monthly and bi-monthly GRACE gravity fields. Comparisons of GRACE-only and combined monthly and bi-monthly solutions show that the striping pattern can only be reduced when using both GOCE observation types (SGG, SST-hl), and mainly between d/o 45 and 60.

Variance estimation in ranked set sampling using a concomitant variable

We propose a nonparametric variance estimator when ranked set sampling (RSS) and judgment post stratification (JPS) are applied by measuring a concomitant variable. Our proposed estimator is obtained by conditioning on observed concomitant values and using nonparametric kernel regression.

Quick divergence but slow convergence during ecotype formation in lake and stream stickleback pairs of variable age

When genetic constraints restrict phenotypic evolution, diversification can be predicted to evolve along so-called lines of least resistance. To address the importance of such constraints and their resolution, studies of parallel phenotypic divergence that differ in their age are valuable. Here, we investigate the parapatric evolution of six lake and stream threespine stickleback systems from Iceland and Switzerland, ranging in age from a few decades to several millennia. Using phenotypic data, we test for parallelism in ecotypic divergence between parapatric lake and stream populations and compare the observed patterns to an ancestral-like marine population. We find strong and consistent phenotypic divergence, both among lake and stream populations and between our freshwater populations and the marine population. Interestingly, ecotypic divergence in low-dimensional phenotype space (i.e. single traits) is rapid and seems to be often completed within 100 years. Yet, the dimensionality of ecotypic divergence was highest in our oldest systems and only there parallel evolution of unrelated ecotypes was strong enough to overwrite phylogenetic contingency. Moreover, the dimensionality of divergence in different systems varies between trait complexes, suggesting different constraints and evolutionary pathways to their resolution among freshwater systems.

Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation.

Eosinophils are white blood cells that function in innate immunity and participate in the pathogenesis of various inflammatory and neoplastic disorders. Their secretory granules contain four cytotoxic proteins, including the eosinophil major basic protein (MBP-1). How MBP-1 toxicity is controlled within the eosinophil itself and activated upon extracellular release is unknown. Here we show how intragranular MBP-1 nanocrystals restrain toxicity, enabling its safe storage, and characterize them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity is triggered by granule acidification, followed by extracellular aggregation, which mediates the damage to pathogens and host cells. Larger non-toxic amyloid plaques are also present in tissues of eosinophilic patients in a feedback mechanism that likely limits tissue damage under pathological conditions of MBP-1 oversecretion. Our results suggest that MBP-1 aggregation is important for innate immunity and immunopathology mediated by eosinophils and clarify how its polymorphic self-association pathways regulate toxicity intra- and extracellularly.

Continuous eclogite melting and variable refertilisation in upwelling heterogeneous mantle

Large-scale tectonic processes introduce a range of crustal lithologies into the Earth's mantle. These lithologies have been implicated as sources of compositional heterogeneity in mantle-derived magmas. The model being explored here assumes the presence of widely dispersed fragments of residual eclogite (derived from recycled oceanic crust), stretched and stirred by convection in the mantle. Here we show with an experimental study that these residual eclogites continuously melt during upwelling of such heterogeneous mantle and we characterize the melting reactions and compositional changes in the residue minerals. The chemical exchange between these partial melts and more refractory peridotite leads to a variably metasomatised mantle. Re-melting of these metasomatised peridotite lithologies at given pressures and temperatures results in diverse melt compositions, which may contribute to the observed heterogeneity of oceanic basalt suites. We also show that heterogeneous upwelling mantle is subject to diverse local freezing, hybridization and carbonate-carbon-silicate redox reactions along a mantle adiabat.

Tubes or sheets: divergent aggregation pathways of an amphiphilic 2,7-substituted pyrene trimer

The self-assembly of an amphiphilic 2,7-linked pyrene trimer in an aqueous environment into two morphologically related forms is described. Supramolecular polymerization leads to the simultaneous formation of nanosheets and nanotubes.

Intraspecific Aggregation Alters Competitive Interactions in Experimental Plant Communities

We tested the prediction from spatial competition models that intraspecific aggregation may promote coexistence and thus maintain biodiversity with experimental communities of four annual species. Monocultures, three-species mixtures, and the four-species mixture were sown at two densities and with either random or intraspecifically aggregated distributions. There was a hierarchy of competitive abilities among the four species. The weaker competitors showed higher aboveground biomass in the aggregated distribution compared to the random distribution, especially at high density. In one species, intraspecific aggregation resulted in an 86% increase in the number of flowering individuals and a 171% increase in the reproductive biomass at high density. The competitively superior species had a lower biomass in the aggregated distribution than in the random distribution at high density. The data support the hypothesis that the spatial distribution of plants profoundly affects competition in such a way that weaker competitors increase their fitness while stronger competitors are suppressed when grown in the neighborhood of conspecifics. This implies that the spatial arrangement of plants in a community can be an important determinant of species coexistence and biodiversity.

Eclogitic diamonds from variable crustal protoliths in the northeastern Siberian craton: trace elements and coupled δ13C – δ18O signatures in diamonds and garnet inclusions

Diamonds of eclogitic assemblages are dominant in the placer diamond deposits of the northeastern Siberian platform. In this study we present new trace elements and stable isotopes (δ13C and δ18O) data for alluvial diamonds and their garnet inclusions from this locality. Cr-rich garnets of peridotitic affinity in the studied diamonds have a narrow range of δ18O values from 5.7‰ to 6.2‰, which is largely overlapping with the accepted mantle range. This narrow range suggests that the garnet inclusions showing different REE patterns and little variations in oxygen isotopes may have formed by different processes involving fluid/melts that, however, were in oxygen isotopic equilibrium with the mantle. The trace element composition of the eclogitic garnet inclusions supports a crustal origin for at least the high-Ca garnets, which show flat HREE patterns and in some cases a positive Eu-anomaly. High-Ca eclogitic garnets generally show heavier oxygen isotope compositions (δ18O 6.5–9.6‰) than what is observed in low-Ca garnets (δ18O 5.7–7.4‰). The variability in oxygen isotopes and trace elements is suggested to be inherited from contrasting crustal protoliths. The relationship between the high δ18O values of inclusions and the low δ13C values of the host diamonds implies that the high-Ca garnet inclusions were derived from intensely hydrated (e.g., δ18O > 7‰) and typically oxidised basaltic rock close to the seawater interface, and that the carbon for diamonds was closely associated with this protolith.