Evidence for the return of subducted continental crust

Author Posting. © Nature Publishing Group, 2007. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 448 (2007): 684-687, doi:10.1038/nature06048.Substantial quantities of terrigenous sediments are known to enter the mantle at subduction zones, but little is known about their fate in the mantle. Subducted sediment may be entrained in buoyantly upwelling plumes and returned to the earth’s surface at hotspots, but the proportion of recycled sediment in the mantle is small and clear examples of recycled sediment in hotspot lavas are rare. We report here remarkably enriched 87Sr/86Sr and 143Nd/144Nd isotope signatures (up to 0.720830 and 0.512285, respectively) in Samoan lavas from three dredge locations on the underwater flanks of Savai’i island, Western Samoa. The submarine Savai’i lavas represent the most extreme 87Sr/86Sr isotope compositions reported for ocean island basalts (OIBs) to date. The data are consistent with the presence of a recycled sediment component (with a composition similar to upper continental crust, or UCC) in the Samoan mantle. Trace element data show similar affinities with UCC—including exceptionally low Ce/Pb and Nb/U ratios—that complement the enriched 87Sr/86Sr and 143Nd/144Nd isotope signatures. The geochemical evidence from the new Samoan lavas radically redefines the composition of the EM2 (enriched mantle 2) mantle endmember, and points to the presence of an ancient recycled UCC component in the Samoan plume

Mycobacterium tuberculosis Complex Mycobacteria as Amoeba-Resistant Organisms

International audienceBackground: Most environmental non-tuberculous mycobacteria have been demonstrated to invade amoebal trophozoites and cysts, but such relationships are largely unknown for members of the Mycobacterium tuberculosis complex. An environmental source has been proposed for the animal Mycobacterium bovis and the human Mycobacterium canettii.Methodology/Principal Findings: Using optic and electron microscopy and co-culture methods, we observed that 89±0.6% of M. canettii, 12.4±0.3% of M. tuberculosis, 11.7±2% of M. bovis and 11.2±0.5% of Mycobacterium avium control organisms were phagocytized by Acanthamoeba polyphaga, a ratio significantly higher for M. canettii (P = 0.03), correlating with the significantly larger size of M. canetti organisms (P = 0.035). The percentage of intraamoebal mycobacteria surviving into cytoplasmic vacuoles was 32±2% for M. canettii, 26±1% for M. tuberculosis, 28±2% for M. bovis and 36±2% for M. avium (P = 0.57). M. tuberculosis, M. bovis and M. avium mycobacteria were further entrapped within the double wall of <1% amoebal cysts, but no M. canettii organisms were observed in amoebal cysts. The number of intracystic mycobacteria was significantly (P = 10−6) higher for M. avium than for the M. tuberculosis complex, and sub-culturing intracystic mycobacteria yielded significantly more (P = 0.02) M. avium organisms (34×104 CFU/mL) than M. tuberculosis (42×101 CFU/mL) and M. bovis (35×101 CFU/mL) in the presence of a washing fluid free of mycobacteria. Mycobacteria survived in the cysts for up to 18 days and cysts protected M. tuberculosis organisms against mycobactericidal 5 mg/mL streptomycin and 2.5% glutaraldehyde.Conclusions/Significance: These data indicate that M. tuberculosis complex organisms are amoeba-resistant organisms, as previously demonstrated for non-tuberculous, environmental mycobacteria. Intercystic survival of tuberculous mycobacteria, except for M. canettii, protect them against biocides and could play a role in their life cycle

Phagosomal Rupture by Mycobacterium tuberculosis Results in Toxicity and Host Cell Death

Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis. Despite significant advances in identifying new immunological parameters associated with mycobacterial disease, some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen-presenting cells are still under debate. To get novel insights into this matter, we used a single-cell fluorescence resonance energy transfer (FRET)-based method to investigate the potential cytosolic access of M. tuberculosis and the resulting cellular consequences in an unbiased, quantitative way. Analysis of thousands of THP-1 macrophages infected with selected wild-type or mutant strains of the M. tuberculosis complex unambiguously showed that M. tuberculosis induced a change in the FRET signal after 3 to 4 days of infection, indicating phagolysosomal rupture and cytosolic access. These effects were not seen for the strains M. tuberculosisΔRD1 or BCG, both lacking the ESX-1 secreted protein ESAT-6, which reportedly shows membrane-lysing properties. Complementation of these strains with the ESX-1 secretion system of M. tuberculosis restored the ability to cause phagolysosomal rupture. In addition, control experiments with the fish pathogen Mycobacterium marinum showed phagolysosomal translocation only for ESX-1 intact strains, further validating our experimental approach. Most importantly, for M. tuberculosis as well as for M. marinum we observed that phagolysosomal rupture was followed by necrotic cell death of the infected macrophages, whereas ESX-1 deletion- or truncation-mutants that remained enclosed within phagolysosomal compartments did not induce such cytotoxicity. Hence, we provide a novel mechanism how ESX-1 competent, virulent M. tuberculosis and M. marinum strains induce host cell death and thereby escape innate host defenses and favor their spread to new cells. In this respect, our results also open new research directions in relation with the extracellular localization of M. tuberculosis inside necrotic lesions that can now be tackled from a completely new perspective

Regulation of expression of Na+,K+-ATPase in androgen-dependent and androgen-independent prostate cancer

The β1-subunit of Na+,K+-ATPase was isolated and identified as an androgen down-regulated gene. Expression was observed at high levels in androgen-independent as compared to androgen-dependent (responsive) human prostate cancer cell lines and xenografts when grown in the presence of androgens. Down-regulation of the β1-subunit was initiated at concentrations between 0.01 nM and 0.03 nM of the synthetic androgen R1881 after relatively long incubation times (> 24 h). Using polyclonal antibodies, the concentration of β1-subunit protein, but not of the α1-subunit protein, was markedly reduced in androgen-dependent human prostate cancer cells (LNCaP-FGC) cultured in the presence of androgens. In line with these observations it was found that the protein expression of total Na+,K+-ATPase in the membrane (measured by 3H-ouabain binding) was also markedly decreased. The main function of Na+,K+-ATPase is to maintain sodium and potassium homeostasis in animal cells. The resulting electrochemical gradient is facilitative for transport of several compounds over the cell membrane (for example cisplatin, a chemotherapeutic agent experimentally used in the treatment of hormone-refractory prostate cancer). Here we observed that a ouabain-induced decrease of Na+,K+-ATPase activity in LNCaP-FGC cells results in reduced sensitivity of these cells to cisplatin-treatment. Surprisingly, androgen-induced decrease of Na+,K+-ATPase expression, did not result in significant protection against the chemotherapeutic agent. © 1999 Cancer Research Campaig

Treatment course and outcomes following drug and alcohol-related traumatic injuries

Both authors are with the NeuroTexas Institute at St. David's HealthCare, St. David's Medical Center, 1015 East 32nd Street, Suite 404, Austin, Texas 78705, USA -- Matthew C. Cowperthwaite is with the Center for Systems and Synthetic Biology, The University of Texas at Austin, 1 University Station, A4800, Austin, Texas 78712, USABackground: Alcohol and drug use is known to be a major factor affecting the incidence of traumatic injury. However, the ways in which immediate pre-injury substance use affects patients' clinical care and outcomes remains unclear. The goal of the present study is to determine the associations between pre-injury use of alcohol or drugs and patient injury severity, hospital course, and clinical outcome. Materials and methods: This study used more than 200,000 records from the National Trauma Data Bank (NTDB), which is the largest trauma registry in the United States. Incidents in the NTDB were placed into one of four classes: alcohol related, drug related, alcohol-and-drug related, and substance negative. Logistic regression models were used to determine comorbid conditions or treatment complications that were significantly associated with pre-injury substance use. Hospital charges were associated with the presence or absence of drugs and alcohol, and patient outcomes were assessed using discharge disposition as delimited by the NTDB. Results: The rates of complications arising during treatment were 8.3, 10.9, 9.9 and 8.6 per one hundred incidents in the alcohol related, drug related, alcohol-and-drug related, and substance-negative classes, respectively. Regression models suggested that pre-injury alcohol use is associated with a 15% higher risk of infection, whereas pre-injury drug use is associated with a 30% higher risk of infection. Pre-injury substance use did not appear to significantly impact clinical outcomes following treatment for traumatic injury, however. Conclusion: This study suggests that pre-injury drug use is associated with a significantly higher complication rate. In particular, infection during hospitalization is a significant risk for both alcohol and drug related trauma visits, and drug-related trauma incidents are associated with increased risk for additional circulatory complications. Although drug and alcohol related trauma incidents are not associated with appreciably worse clinical outcomes, patients experiencing such complications are associated with significantly greater length of stay and higher hospitalization costs. Therefore significant benefits to trauma patients could be gained with enhanced surveillance for pre-injury substance use upon admission to the ED, and closer monitoring for infection or circulatory complications during their period of hospitalization.Center for Systems and Synthetic [email protected]

Mycobacterium tuberculosis Induces an Atypical Cell Death Mode to Escape from Infected Macrophages

BACKGROUND: Macrophage cell death following infection with Mycobacterium tuberculosis plays a central role in tuberculosis disease pathogenesis. Certain attenuated strains induce extrinsic apoptosis of infected macrophages but virulent strains of M. tuberculosis suppress this host response. We previously reported that virulent M. tuberculosis induces cell death when bacillary load exceeds approximately 20 per macrophage but the precise nature of this demise has not been defined. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed the characteristics of cell death in primary murine macrophages challenged with virulent or attenuated M. tuberculosis complex strains. We report that high intracellular bacillary burden causes rapid and primarily necrotic death via lysosomal permeabilization, releasing hydrolases that promote Bax/Bak-independent mitochondrial damage and necrosis. Cell death was independent of cathepsins B or L and notable for ultrastructural evidence of damage to lipid bilayers throughout host cells with depletion of several host phospholipid species. These events require viable bacteria that can respond to intracellular cues via the PhoPR sensor kinase system but are independent of the ESX1 system. CONCLUSIONS/SIGNIFICANCE: Cell death caused by virulent M. tuberculosis is distinct from classical apoptosis, pyroptosis or pyronecrosis. Mycobacterial genes essential for cytotoxicity are regulated by the PhoPR two-component system. This atypical death mode provides a mechanism for viable bacilli to exit host macrophages for spreading infection and the eventual transition to extracellular persistence that characterizes advanced pulmonary tuberculosis

Arc magmas sourced from melange diapirs in subduction zones

Author Posting. © The Author(s), 2012. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Geoscience 5 (2012): 862-867, doi:10.1038/ngeo1634.At subduction zones, crustal material is recycled back into the mantle. A certain proportion, however, is returned to the overriding plate via magmatism. The magmas show a characteristic range of compositions that have been explained by three-component mixing in their source regions: hydrous fluids derived from subducted altered oceanic crust and components derived from the thin sedimentary veneer are added to the depleted peridotite in the mantle beneath the volcanoes. However, currently no uniformly accepted model exists for the physical mechanism that mixes the three components and transports them from the slab to the magma source. Here we present an integrated physico-chemical model of subduction zones that emerges from a review of the combined findings of petrology, modelling, geophysics, and geochemistry: Intensely mixed metamorphic rock formations, so-called mélanges, form along the slab-mantle interface and comprise the characteristic trace-element patterns of subduction-zone magmatic rocks. We consider mélange formation the physical mixing process that is responsible for the geochemical three-component pattern of the magmas. Blobs of low-density mélange material, so-called diapirs, rise buoyantly from the surface of the subducting slab and provide a means of transport for well-mixed materials into the mantle beneath the volcanoes, where they produce melt. Our model provides a consistent framework for the interpretation of geophysical, petrological and geochemical data of subduction zones.H.M. was funded by the J. LamarWorzel Assistant Scientist Fund and the Penzance Endowed Fund in Support of Assistant Scientists. Funding from NSF grant #1119403 (G. Harlow) is acknowledged.2013-05-1

Kimberlites reveal 2.5-billion-year evolution of a deep, isolated mantle reservoir

The widely accepted paradigm of Earth's geochemical evolution states that the successive extraction of melts from the mantle over the past 4.5 billion years formed the continental crust, and produced at least one complementary melt-depleted reservoir that is now recognized as the upper-mantle source of mid-ocean-ridge basalts1. However, geochemical modelling and the occurrence of high 3He/4He (that is, primordial) signatures in some volcanic rocks suggest that volumes of relatively undifferentiated mantle may reside in deeper, isolated regions2. Some basalts from large igneous provinces may provide temporally restricted glimpses of the most primitive parts of the mantle3,4, but key questions regarding the longevity of such sources on planetary timescales—and whether any survive today—remain unresolved. Kimberlites, small-volume volcanic rocks that are the source of most diamonds, offer rare insights into aspects of the composition of the Earth’s deep mantle. The radiogenic isotope ratios of kimberlites of different ages enable us to map the evolution of this domain through time. Here we show that globally distributed kimberlites originate from a single homogeneous reservoir with an isotopic composition that is indicative of a uniform and pristine mantle source, which evolved in isolation over at least 2.5 billion years of Earth history—to our knowledge, the only such reservoir that has been identified to date. Around 200 million years ago, extensive volumes of the same source were perturbed, probably as a result of contamination by exogenic material. The distribution of affected kimberlites suggests that this event may be related to subduction along the margin of the Pangaea supercontinent. These results reveal a long-lived and globally extensive mantle reservoir that underwent subsequent disruption, possibly heralding a marked change to large-scale mantle-mixing regimes. These processes may explain why uncontaminated primordial mantle is so difficult to identify in recent mantle-derived melts

The association between balance and free-living physical activity in an older community-dwelling adult population: a systematic review and meta-analysis

Abstract Background Poor balance is associated with an increased risk of falling, disability and death in older populations. To better inform policies and help reduce the human and economic cost of falls, this novel review explores the effects of free-living physical activity on balance in older (50 years and over) healthy community-dwelling adults. Methods Search methods: CENTRAL, Bone, Joint and Muscle Trauma Group Specialised register and CDSR in the Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, and AMED were searched from inception to 7th June 2016. Selection criteria: Intervention and observational studies investigating the effects of free-living PA on balance in healthy community-dwelling adults (50 years and older). Data extraction and analysis: Thirty studies were eligible for inclusion. Data extraction and risk of bias assessment were independently carried out by two review authors. Due to the variety of outcome measures used in studies, balance outcomes from observational studies were pooled as standardised mean differences or mean difference where appropriate and 95% confidence intervals, and outcomes from RCTs were synthesised using a best evidence approach. Results Limited evidence provided by a small number of RCTs, and evidence from observational studies of moderate methodological quality, suggest that free-living PA of between one and 21 years’ duration improves measures of balance in older healthy community-dwelling adults. Statistical analysis of observational studies found significant effects in favour of more active groups for neuromuscular measures such as gait speed; functionality using Timed Up and Go, Single Leg Stance, and Activities of Balance Confidence Scale; flexibility using the forward reach test; and strength using the isometric knee extension test and ultrasound. A significant effect was also observed for less active groups on a single sensory measure of balance, the knee joint repositioning test. Conclusion There is some evidence that free-living PA is effective in improving balance outcomes in older healthy adults, but future research should include higher quality studies that focus on a consensus of balance measures that are clinically relevant and explore the effects of free-living PA on balance over the longer-term