812 research outputs found

    Are all sediment traps created equal? An intercomparison study of carbon export methodologies at the PAP-SO site

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    Sinking particulate flux out of the upper ocean is a key observation of the ocean’s biological carbon cycle. Particle flux in the upper mesopelagic is often determined using sediment traps but there is no absolute standard for the measurement. Prior to this study, differing neutrally-buoyant sediment trap designs have not been deployed simultaneously, which precludes meaningful comparisons between flux data collected using these designs. The aim of the study was to compare a suite of modern methods for measuring sinking carbon flux out of the surface ocean. This study compared samples from two neutrally buoyant drifting sediment trap designs, and a surface tethered drifting sediment trap, which collected sinking particles alongside other methods for sampling particle properties, including in situ pumps and 234Th radionuclide measurements. Samples were collected at the Porcupine Abyssal Plain Sustained Observatory (PAP-SO) site in the Northeast Atlantic Ocean (49°N, 16.5°W). Neutrally-buoyant conical traps appeared to collect lower absolute fluxes than neutrally-buoyant, or surface-tethered cylindrical traps, but compositional ratios of sinking particles indicated collection of similar material when comparing the conical and cylindrical traps. In situ pump POC:234Th ratios generally agreed with trap ratios but conical trap samples were somewhat depleted in 234Th, which along with sinking particle size distribution data determined from gel traps, may imply under-sampling of small particles. Cylindrical trap POC fluxes were of similar magnitude to 234Th-derived POC fluxes while conical POC fluxes were lower. Further comparisons are needed to distinguish if differences in particle flux magnitude are due to conical versus cylindrical trap designs. Parallel analytical determinations, conducted by different laboratories, of replicate samples for elemental fluxes and gel trap particle size distributions were comparable. This study highlights that the magnitude of particle fluxes and size spectra may be more sensitive than the chemical composition of particle fluxes to the instrumentation used. Only two deployments were possible during this study so caution should be taken when applying these findings to other regions and export regimes. We recommend that multiple methodologies to measure carbon export should be employed in field studies, to better account for each method’s merits and uncertainties. These discrepancies need further study to allow carbon export fluxes to be compared with confidence across laboratory, region and time and to achieve an improved global understanding of processes driving and controlling carbon export

    Manipulating adenovirus hexon hypervariable loops dictates immune neutralisation and coagulation factor X-dependent cell interaction in vitro and in vivo

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    Adenoviruses are common pathogens, mostly targeting ocular, gastrointestinal and respiratory cells, but in some cases infection disseminates, presenting in severe clinical outcomes. Upon dissemination and contact with blood, coagulation factor X (FX) interacts directly with the adenovirus type 5 (Ad5) hexon. FX can act as a bridge to bind heparan sulphate proteoglycans, leading to substantial Ad5 hepatocyte uptake. FX “coating” also protects the virus from host IgM and complement-mediated neutralisation. However, the contribution of FX in determining Ad liver transduction whilst simultaneously shielding the virus from immune attack remains unclear. In this study, we demonstrate that the FX protection mechanism is not conserved amongst Ad types, and identify the hexon hypervariable regions (HVR) of Ad5 as the capsid proteins targeted by this host defense pathway. Using genetic and pharmacological approaches, we manipulate Ad5 HVR interactions to interrogate the interplay between viral cell transduction and immune neutralisation. We show that FX and inhibitory serum components can co-compete and virus neutralisation is influenced by both the location and extent of modifications to the Ad5 HVRs. We engineered Ad5-derived HVRs into the rare, native non FX-binding Ad26 to create Ad26.HVR5C. This enabled the virus to interact with FX at high affinity, as quantified by surface plasmon resonance, FX-mediated cell binding and transduction assays. Concomitantly, Ad26.HVR5C was also sensitised to immune attack in the absence of FX, a direct consequence of the engineered HVRs from Ad5. In both immune competent and deficient animals, Ad26.HVR5C hepatic gene transfer was mediated by FX following intravenous delivery. This study gives mechanistic insight into the pivotal role of the Ad5 HVRs in conferring sensitivity to virus neutralisation by IgM and classical complement-mediated attack. Furthermore, through this gain-of-function approach we demonstrate the dual functionality of FX in protecting Ad26.HVR5C against innate immune factors whilst determining liver targeting

    Fatal meningitis in a previously healthy young adult caused by Streptococcus pneumoniae serotype 38: an emerging serotype?

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    BACKGROUND: In December 2001, a fatal case of pneumococcal meningitis in a Marine Corps recruit was identified. As pneumococcal vaccine usage in recruit populations is being considered, an investigation was initiated into the causative serotype. CASE PRESENTATION: Traditional and molecular methods were utilized to determine the serotype of the infecting pneumococcus. The pneumococcal isolate was identified as serotype 38 (PS38), a serotype not covered by current vaccine formulations. The global significance of this serotype was explored in the medical literature, and found to be a rare but recognized cause of carriage and invasive disease. CONCLUSION: The potential of PS38 to cause severe disease is documented in this report. Current literature does not support the hypothesis that this serotype is increasing in incidence. However, as we monitor the changing epidemiology of pneumococcal illness in the US in this conjugate era, PS38 might find a more prominent and concerning niche as a replacement serotype

    Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline

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    <b>Objective</b>: MicroRNAs (miRNAs) are small noncoding RNAs that have the capacity to control protein production through binding "seed" sequences within a target mRNA. Each miRNA is capable of potentially controlling hundreds of genes. The regulation of miRNAs in the lung during the development of pulmonary arterial hypertension (PAH) is unknown.<p></p> <b>Methods and Results</b>: We screened lung miRNA profiles in a longitudinal and crossover design during the development of PAH caused by chronic hypoxia or monocrotaline in rats. We identified reduced expression of Dicer, involved in miRNA processing, during the onset of PAH after hypoxia. MiR-22, miR-30, and let-7f were downregulated, whereas miR-322 and miR-451 were upregulated significantly during the development of PAH in both models. Differences were observed between monocrotaline and chronic hypoxia. For example, miR-21 and let-7a were significantly reduced only in monocrotaline-treated rats. MiRNAs that were significantly regulated were validated by quantitative polymerase chain reaction. By using in vitro studies, we demonstrated that hypoxia and growth factors implicated in PAH induced similar changes in miRNA expression. Furthermore, we confirmed miR-21 downregulation in human lung tissue and serum from patients with idiopathic PAH.<p></p> <b>Conclusion</b>: Defined miRNAs are regulated during the development of PAH in rats. Therefore, miRNAs may contribute to the pathogenesis of PAH and represent a novel opportunity for therapeutic intervention.<p></p&gt

    An implementation plan for priorities in solar-system space physics

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    The scientific objectives and implementation plans and priorities of the Space Science Board in areas of solar physics, heliospheric physics, magnetospheric physics, upper atmosphere physics, solar-terrestrial coupling, and comparative planetary studies are discussed and recommended programs are summarized. Accomplishments of Skylab, Solar Maximum Mission, Nimbus-7, and 11 other programs are highlighted. Detailed mission plans in areas of solar and heliospheric physics, plasma physics, and upper atmospheric physics are also described

    Onset of experimental severe cardiac fibrosis is mediated by overexpression of angiotensin-converting enzyme 2

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    Angiotensin-converting enzyme (ACE) 2 is a recently identified homologue of ACE. There is great interest in the therapeutic benefit for ACE2 overexpression in the heart. However, the role of ACE2 in the regulation of cardiac structure and function, as well as maintenance of systemic blood pressure, remains poorly understood. In cell culture, ACE2 overexpression led to markedly increased myocyte volume, assessed in primary rabbit myocytes. To assess ACE2 function in vivo, we used a recombinant adeno-associated virus 6 delivery system to provide 11-week overexpression of ACE2 in the myocardium of stroke-prone spontaneously hypertensive rats. ACE2, as well as the ACE inhibitor enalapril, significantly reduced systolic blood pressure. However, in the heart, ACE2 overexpression resulted in cardiac fibrosis, as assessed by histological analysis with concomitant deficits in ejection fraction and fractional shortening measured by echocardiography. Furthermore, global gene expression profiling demonstrated the activation of profibrotic pathways in the heart mediated by ACE2 gene delivery. This study demonstrates that sustained overexpression of ACE2 in the heart in vivo leads to the onset of severe fibrosis

    A Randomized Controlled Trial of Whole Body Vibration Exposure on Markers of Bone Turnover in Postmenopausal Women

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    Purpose. To examine the effects of two doses of low-frequency (12 Hz), low-magnitude (0.3 g), whole body vibration on markers of bone formation and resorption in postmenopausal women. Methods. Women were recruited and randomized into a sham vibration control group, one time per week vibration group (1×/week), or three times per week vibration group (3×/week). Vibration exposure consisted of 20 minutes of intermittent vibration for the 1×/week and 3×/week groups, and sham vibration (<0.1 g) for the control group for eight weeks. Double-blinded primary outcome measures were urine markers of bone resorption: N-telopeptide X normalised to creatinine (NTx/Cr) and bone formation: bone-specific alkaline phosphatase (ALP). Results. Forty-six women (59.8 ± 6.2 years, median 7.3 years since menopause) were enrolled. NTx/Cr was significantly reduced (34.6%) in the 3×/wk vibration group but not in the 1×/wk vibration group compared with sham control (P < .01) group. No effect of time or group allocation was observed on the bone formation marker ALP (P = .27). Conclusion. We have shown for the first time that low-frequency, low-magnitude vibration 3×/week for eight weeks in postmenopausal women results in a significant reduction in NTx/Cr, a marker of bone resorption, when compared with sham vibration exposure

    Ozone depletion, greenhouse gases, and climate change

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    This symposium was organized to study the unusual convergence of a number of observations, both short and long term that defy an integrated explanation. Of particular importance are surface temperature observations and observations of upper atmospheric temperatures, which have declined significantly in parts of the stratosphere. There has also been a dramatic decline in ozone concentration over Antarctica that was not predicted. Significant changes in precipitation that seem to be latitude dependent have occurred. There has been a threefold increase in methane in the last 100 years; this is a problem because a source does not appear to exist for methane of the right isotopic composition to explain the increase. These and other meteorological global climate changes are examined in detail
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