Advances in measurements of particle cycling and fluxes in the ocean

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution February 2013The sinking flux of particles is an important removal mechanism of carbon from the surface ocean as part of the biological pump and can play a role in cycling of other chemical species. This work dealt with improving methods of measuring particle export and measuring export on different scales to assess its spatial variability. First, the assumption of 238U linearity with salinity, used in the 238U–234Th method, was reevaluated using a large sample set over a wide salinity range. Next, neutrally buoyant and surface-tethered sediment traps were compared during a three-year time series in the subtropical Atlantic. This study suggested that previously observed imbalances between carbon stocks and fluxes in this region are not due to undersampling by traps. To assess regional variability of particle export, surface and water-column measurements of 234Th were combined for the first time to measure fluxes on ~20 km scales. Attempts to relate surface properties to particle export were complicated by the temporal decoupling of production and export. Finally, particle export from 234Th was measured on transects of the Atlantic Ocean to evaluate basin-scale export variability. High-resolution sampling through the water-column allowed for the identification of unique 234Th features in the intermediate water column.I was supported by NASA Headquarters under the NASA Earth and Space Science Fellowship Program (Grant NNX10AO72H). Specific projects were funded by grants from the National Science Foundation, including Carbon Flux Through the Twilight Zone – New Tools to Measure Change (OCE-0628416), WAPflux – New Tools to Study the Fates of Phytoplankton Production in the West Antarctic Peninsula (ANT-0838866), and GEOTRACES Atlantic Section: Trace Element Sources and Sinks Elucidated by Short- Lived Radium and Thorium Isotopes (OCE-0925158)

Transduction of rat pancreatic islets with pseudotyped adeno-associated virus vectors

<p>Abstract</p> <p>Background</p> <p>Pancreatic islet transplantation is a promising treatment for type I diabetes mellitus, but current immunosuppressive strategies do not consistently provide long-term survival of transplanted islets. We are therefore investigating the use of adeno-associated viruses (AAVs) as gene therapy vectors to transduce rat islets with immunosuppressive genes prior to transplantation into diabetic mice.</p> <p>Results</p> <p>We compared the transduction efficiency of AAV2 vectors with an AAV2 capsid (AAV2/2) to AAV2 vectors pseudotyped with AAV5 (AAV2/5), AAV8 (AAV2/8) or bovine adeno-associated virus (BAAV) capsids, or an AAV2 capsid with an insertion of the low density lipoprotein receptor ligand from apolipoprotein E (AAV2apoE), on cultured islets, in the presence of helper adenovirus infection to speed expression of a GFP transgene. Confocal microscopy and flow cytometry were used. The AAV2/5 vector was superior to AAV2/2 and AAV2/8 in rat islets. Flow cytometry indicated AAV2/5-mediated gene expression in approximately 9% of rat islet cells and almost 12% of insulin-positive cells. The AAV2/8 vector had a higher dependence on the helper virus multiplicity of infection than the AAV 2/5 vector. In addition, the BAAV and AAV2apoE vectors were superior to AAV2/2 for transducing rat islets. Rat islets (300 per mouse) transduced with an AAV2/5 vector harboring the immunosuppressive transgene, <it>tgfβ1</it>, retain the ability to correct hyperglycemia when transplanted into immune-deficient diabetic mice.</p> <p>Conclusion</p> <p>AAV2/5 vectors may therefore be useful for pre-treating donor islets prior to transplantation.</p

Annual variations in the near-Earth solar wind

Earth’s orbit and rotation produces systematic variations in geomagnetic activity, most notably via the changing orientation of the dayside magnetospheric magnetic field with respect to the heliospheric magnetic field (HMF). Aside from these geometric effects, it is generally assumed that the solar wind in near-Earth is uniformly sampled. But systematic changes in the intrinsic solar wind conditions in near-Earth space could arise due to the annual variations in Earth heliocentric distance and heliographic latitude. In this study, we use 24 years of Advanced Composition Explorer data to investigate the annual variations in the scalar properties of the solar wind, namely the solar wind proton density, the radial solar wind speed and the HMF intensity. All parameters do show some degree of systematic annual variation, with amplitudes of around 10 to 20%. For HMF intensity, the variation is in phase with the Earth’s heliocentric distance variation, and scaling observations for distance largely explains the observed variation. For proton density and solar wind speed, however, the phase of the annual variation is inconsistent with Earth’s heliocentric distance. Instead, we attribute the variations in speed and density to Earth’s heliographic latitude variation and systematic sampling of higher speed solar wind at higher latitudes. Indeed, these annual variations are most strongly ordered at solar minimum. Conversely, combining scalar solar wind parameters to produce estimates of dynamic pressure and potential power input to the magnetosphere results in solar maximum exhibiting a greater annual variation, with an amplitude of around 40%. This suggests Earth’s position in the heliosphere makes a significant contribution to annual variations in space weather, in addition to the already well-studied geometric effects

An Anti-Human ICAM-1 Antibody Inhibits Rhinovirus-Induced Exacerbations of Lung Inflammation

Human rhinoviruses (HRV) cause the majority of common colds and acute exacerbations of asthma and chronic obstructive pulmonary disease (COPD). Effective therapies are urgently needed, but no licensed treatments or vaccines currently exist. Of the 100 identified serotypes, ∼90% bind domain 1 of human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor, making this an attractive target for development of therapies; however, ICAM-1 domain 1 is also required for host defence and regulation of cell trafficking, principally via its major ligand LFA-1. Using a mouse anti-human ICAM-1 antibody (14C11) that specifically binds domain 1 of human ICAM-1, we show that 14C11 administered topically or systemically prevented entry of two major groups of rhinoviruses, HRV16 and HRV14, and reduced cellular inflammation, pro-inflammatory cytokine induction and virus load in vivo. 14C11 also reduced cellular inflammation and Th2 cytokine/chemokine production in a model of major group HRV-induced asthma exacerbation. Interestingly, 14C11 did not prevent cell adhesion via human ICAM-1/LFA-1 interactions in vitro, suggesting the epitope targeted by 14C11 was specific for viral entry. Thus a human ICAM-1 domain-1-specific antibody can prevent major group HRV entry and induction of airway inflammation in vivo

Variability in efficiency of particulate organic carbon export: A model study

The flux of organic carbon from the surface ocean to mesopelagic depths is a key component of the global carbon cycle and is ultimately derived from primary production (PP) by phytoplankton. Only a small fraction of organic carbon produced by PP is exported from the upper ocean, referred to as the export efficiency (herein e-ratio). Limited observations of the e-ratio are available and there is thus considerable interest in using remotely-sensed parameters such as sea surface temperature to extrapolate local estimates to global annual export flux. Currently, there are large discrepancies between export estimates derived in this way; one possible explanation is spatial or temporal sampling bias in the observations. Here we examine global patterns in the spatial and seasonal variability in e-ratio and the subsequent effect on export estimates using a high resolution global biogeochemical model. NEMO-MEDUSA represents export as separate slow and fast sinking detrital material whose remineralisation is respectively temperature dependent and a function of ballasting minerals. We find that both temperature and the fraction of export carried by slow sinking particles are factors in determining e-ratio, suggesting that current empirical algorithms for e-ratio that only consider temperature are overly simple. We quantify the temporal lag between PP and export, which is greatest in regions of strong variability in PP where seasonal decoupling can result in large e-ratio variability. Extrapolating global export estimates from instantaneous measurements of e-ratio is strongly affected by seasonal variability, and can result in errors in estimated export of up to ±60%

Review of methods for detecting glycemic disorders

Prediabetes (intermediate hyperglycemia) consists of two abnormalities, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) detected by a standardized 75-gram oral glucose tolerance test (OGTT). Individuals with isolated IGT or combined IFG and IGT have increased risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). Diagnosing prediabetes early and accurately is critical in order to refer high-risk individuals for intensive lifestyle modification. However, there is currently no international consensus for diagnosing prediabetes with HbA1c or glucose measurements based upon American Diabetes Association (ADA) and the World Health Organization (WHO) criteria that identify different populations at risk for progressing to diabetes. Various caveats affecting the accuracy of interpreting the HbA1c including genetics complicate this further. This review describes established methods for detecting glucose disorders based upon glucose and HbA1c parameters as well as novel approaches including the 1-hour plasma glucose (1-h PG), glucose challenge test (GCT), shape of the glucose curve, genetics, continuous glucose monitoring (CGM), measures of insulin secretion and sensitivity, metabolomics, and ancillary tools such as fructosamine, glycated albumin (GA), 1,5- anhydroglucitol (1,5-AG). Of the approaches considered, the 1-h PG has considerable potential as a biomarker for detecting glucose disorders if confirmed by additional data including health economic analysis. Whether the 1-h OGTT is superior to genetics and omics in providing greater precision for individualized treatment requires further investigation. These methods will need to demonstrate substantially superiority to simpler tools for detecting glucose disorders to justify their cost and complexity

Divergent responses of viral and bacterial communities in the gut microbiome to dietary disturbances in mice

To improve our understanding of the stability of mammalian intestinal communities, we characterized the responses of both bacterial and viral communities in murine fecal samples to dietary changes between high- and low-fat (LF) diets. Targeted DNA extraction methods for bacteria, virus-like particles and induced prophages were used to generate bacterial and viral metagenomes as well as 16S ribosomal RNA amplicons. Gut microbiome communities from two cohorts of C57BL/6 mice were characterized in a 6-week diet perturbation study in response to high fiber, LF and high-refined sugar, milkfat (MF) diets. The resulting metagenomes from induced bacterial prophages and extracellular viruses showed significant overlap, supporting a largely temperate viral lifestyle within these gut microbiomes. The resistance of baseline communities to dietary disturbances was evaluated, and we observed contrasting responses of baseline LF and MF bacterial and viral communities. In contrast to baseline LF viral communities and bacterial communities in both diet treatments, baseline MF viral communities were sensitive to dietary disturbances as reflected in their non-recovery during the washout period. The contrasting responses of bacterial and viral communities suggest that these communities can respond to perturbations independently of each other and highlight the potentially unique role of viruses in gut health

Self-reported dental hygiene, obesity, and systemic inflammation in a pediatric rural community cohort

Background A growing body of epidemiologic evidence links oral health, obesity, and cardiovascular health, though few studies have reported on these relationships in children. While underlying mechanisms are unclear, adult studies have suggested sub-acute systemic inflammation, also implicated in the etiology of both obesity and cardiovascular disease. This study investigated associations between self-reported dental hygiene, obesity, and systemic inflammation in children. Methods 128 children \u3c 19 years of age from rural counties in West Virginia participated in a community-based health screening that included anthropometric assessments, blood collection, and a questionnaire about dental hygiene and self-assessed oral health. Results Participants ranged from 3.0-18.7 years. Univariate analysis demonstrated an association between parent-reported dental hygiene, including frequency of preventive dental care and parent-assessed overall dental health, and markers of systemic inflammation but not obesity. In multivariable regression, parent-assessed overall dental health and obesity were independent predictors of systemic inflammation, after adjustment for age, gender, and parent education. Conclusions This is the first known study of the association between dental hygiene, obesity, and systemic inflammation in children. These results highlight the importance of preventive dental care in overall, systemic health in children and are consistent with previous reports in adults

Genome-Wide Association Study Implicates Chromosome 9q21.31 as a Susceptibility Locus for Asthma in Mexican Children

Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case–parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10×10−6 in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79×10−7). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma