Cosmogenic 26Al/10Be surface production ratio in Greenland

The assumed value for the cosmogenic 26Al/10Be surface production rate ratio in quartz is an important parameter for studies investigating the burial or subaerial erosion of long-lived surfaces and sediments. Recent models and data suggest that the production ratio is spatially variable and may be greater than originally thought. Here we present measured 26Al/10Be ratios for 24 continuously exposed bedrock and boulder surfaces spanning ~61–77°N in Greenland. Empirical measurements, such as ours, include nuclides produced predominately by neutron-induced spallation with percent-level contributions by muon interactions. The slope of a York regression line fit to our data is 7.3 ± 0.3 (1σ), suggesting that the 26Al/10Be surface production ratio exceeds the commonly used value of 6.75, at least in the Arctic. A higher 26Al/10Be production ratio has implications for multinuclide cosmogenic isotope studies because it results in greater modeled burial durations and erosion rates

History of clinical transplantation

The emergence of transplantation has seen the development of increasingly potent immunosuppressive agents, progressively better methods of tissue and organ preservation, refinements in histocompatibility matching, and numerous innovations is surgical techniques. Such efforts in combination ultimately made it possible to successfully engraft all of the organs and bone marrow cells in humans. At a more fundamental level, however, the transplantation enterprise hinged on two seminal turning points. The first was the recognition by Billingham, Brent, and Medawar in 1953 that it was possible to induce chimerism-associated neonatal tolerance deliberately. This discovery escalated over the next 15 years to the first successful bone marrow transplantations in humans in 1968. The second turning point was the demonstration during the early 1960s that canine and human organ allografts could self-induce tolerance with the aid of immunosuppression. By the end of 1962, however, it had been incorrectly concluded that turning points one and two involved different immune mechanisms. The error was not corrected until well into the 1990s. In this historical account, the vast literature that sprang up during the intervening 30 years has been summarized. Although admirably documenting empiric progress in clinical transplantation, its failure to explain organ allograft acceptance predestined organ recipients to lifetime immunosuppression and precluded fundamental changes in the treatment policies. After it was discovered in 1992 that long-surviving organ transplant recipient had persistent microchimerism, it was possible to see the mechanistic commonality of organ and bone marrow transplantation. A clarifying central principle of immunology could then be synthesized with which to guide efforts to induce tolerance systematically to human tissues and perhaps ultimately to xenografts

Effect of preoperative thoracic duct drainage on canine kidney transplantation

Chronic drainage of the thoracic duct to the esophagus was developed in dogs, and its efficacy in immunomodulation was tested using kidney transplantation. Compared to 9.7 days in the control, the mean animal survival was prolonged to 9.9 days, 17.8 days, and 18.5 days when TDD was applied preoperatively for 3 weeks, 6 weeks, and 9 weeks, respectively. Prolongation was significant after 6 weeks. Patency of the fistula was 93.5, 80.4, and 76.1% at respective weeks. Number of peripheral T-lymphocytes determined by a new monoclonal antibody diminished after 3 weeks. All animals were in normal health, requiring no special care for fluid, electrolyte, or protein replacement

Near-infrared spectro-interferometry of three OH/IR Stars with the VLTI/AMBER instrument

We investigate the molecular and dusty environment of OH/IR stars in order to characterize the mass-loss process during the tip-AGB superwind phase. Employing the AMBER instrument at the VLT Interferometer we obtained near-infrared H- and K-band spectro-interferometric observations of the three OH/IR stars IRAS 13479-5436, IRAS 14086-6907 and IRAS 17020-5254 with a spectral resolution of about 35. We use a two-component geometrical model, consisting of a uniform disk and a Gaussian disk, to obtain characteristic angular sizes of the central stellar sources and their dust envelopes, as well as the flux ratios between these components. Angular uniform disk diameters of the three central components of the objects above have values between 3.2 mas and 5.4 mas. For their dust envelopes, we find FWHM values between 17.1 mas and 25.2 mas. According to distance estimates from the literature, the central stellar components have radii between 900 R_sun and 1400 R_sun, while their dust envelopes reach FWHM values between 9000 R_sun and 13000 R_sun. The visibility functions of all three sources exhibit wavelength variations that resemble those of earlier VLTI/AMBER observations of semi-regular and Mira variable AGB stars. These are interpreted as characteristic of atmospheric molecular layers lying above the photosphere. We also find that the dust envelopes have a clearly larger optical depth than those known for Mira stars. We interpret this as an expected result of the "superwind" phase, the final 10 000 to 30 000 years of AGB-evolution, when the mass-loss rate increases by a factor of 10-100. By their different optical depths, the three dust shells studied here may represent different stages of the "superwind" and different initial masses.Comment: 5 pages, 6 figures, accepted for publication in Astronomy and Astrophysic

Dopamine transporter (DAT1) and dopamine receptor D4 (DRD4) genotypes differentially impact on electrophysiological correlates of error processing

Peer reviewedPublisher PD

Occupational exposure to chemicals and fetal growth: the Generation R Study

Background Developmental diseases, such as birth defects, growth restriction and preterm delivery, account for >25 of infant mortality and morbidity. Several studies have shown that exposure to chemicals during pregnancy is associated with adverse birth outcomes. The aim of this study was to identify whether occupational exposure to various chemicals might adversely influence intrauterine growth patterns and placental weight.Methods Associations between mat

Mitochondrial Genome Sequences Effectively Reveal the Phylogeny of Hylobates Gibbons

BACKGROUND: Uniquely among hominoids, gibbons exist as multiple geographically contiguous taxa exhibiting distinctive behavioral, morphological, and karyotypic characteristics. However, our understanding of the evolutionary relationships of the various gibbons, especially among Hylobates species, is still limited because previous studies used limited taxon sampling or short mitochondrial DNA (mtDNA) sequences. Here we use mtDNA genome sequences to reconstruct gibbon phylogenetic relationships and reveal the pattern and timing of divergence events in gibbon evolutionary history. METHODOLOGY/PRINCIPAL FINDINGS: We sequenced the mitochondrial genomes of 51 individuals representing 11 species belonging to three genera (Hylobates, Nomascus and Symphalangus) using the high-throughput 454 sequencing system with the parallel tagged sequencing approach. Three phylogenetic analyses (maximum likelihood, Bayesian analysis and neighbor-joining) depicted the gibbon phylogenetic relationships congruently and with strong support values. Most notably, we recover a well-supported phylogeny of the Hylobates gibbons. The estimation of divergence times using Bayesian analysis with relaxed clock model suggests a much more rapid speciation process in Hylobates than in Nomascus. CONCLUSIONS/SIGNIFICANCE: Use of more than 15 kb sequences of the mitochondrial genome provided more informative and robust data than previous studies of short mitochondrial segments (e.g., control region or cytochrome b) as shown by the reliable reconstruction of divergence patterns among Hylobates gibbons. Moreover, molecular dating of the mitogenomic divergence times implied that biogeographic change during the last five million years may be a factor promoting the speciation of Sundaland animals, including Hylobates species

Pathogenic mycobacteria achieve cellular persistence by inhibiting the Niemann-Pick Type C disease cellular pathway

Background. Tuberculosis remains a major global health concern. The ability to prevent phagosome-lysosome fusion is a key mechanism by which intracellular mycobacteria, including Mycobacterium tuberculosis, achieve long-term persistence within host cells. The mechanisms underpinning this key intracellular pro-survival strategy remain incompletely understood. Host macrophages infected with intracellular mycobacteria share phenotypic similarities with cells taken from patients suffering from Niemann-Pick Disease Type C (NPC), a rare lysosomal storage disease in which endocytic trafficking defects and lipid accumulation within the lysosome lead to cell dysfunction and cell death. We investigated whether these shared phenotypes reflected an underlying mechanistic connection between mycobacterial intracellular persistence and the host cell pathway dysfunctional in NPC.  Methods. The induction of NPC phenotypes in macrophages from wild-type mice or obtained from healthy human donors was assessed via infection with mycobacteria and subsequent measurement of lipid levels and intracellular calcium homeostasis. The effect of NPC therapeutics on intracellular mycobacterial load was also assessed.  Results. Macrophages infected with intracellular mycobacteria phenocopied NPC cells, exhibiting accumulation of multiple lipid types, reduced lysosomal Ca 2+ levels, and defects in intracellular trafficking. These NPC phenotypes could also be induced using only lipids/glycomycolates from the mycobacterial cell wall. These data suggest that intracellular mycobacteria inhibit the NPC pathway, likely via inhibition of the NPC1 protein, and subsequently induce altered acidic store Ca 2+ homeostasis. Reduced lysosomal calcium levels may provide a mechanistic explanation for the reduced levels of phagosome-lysosome fusion in mycobacterial infection. Treatments capable of correcting defects in NPC mutant cells via modulation of host cell calcium were of benefit in promoting clearance of mycobacteria from infected host cells.  Conclusion. These findings provide a novel mechanistic explanation for mycobacterial intracellular persistence, and suggest that targeting interactions between the mycobacteria and host cell pathways may provide a novel avenue for development of anti-TB therapies