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  • 1
    Publication Date: 2020-07-30
    Description: To explore the transport of carbon into water masses from the surface ocean to depths of ∼1000 m∼1000 m in the southwest Pacific Ocean, we generated time series of radiocarbon (View the MathML sourceΔC14) from fish otoliths. Otoliths (carbonate earstones) from long-lived fish provide an indirect method to examine the “bomb pulse” of radiocarbon that originated in the 1950s and 1960s, allowing identification of changes to distributions of 14C that has entered and mixed within the ocean. We micro-sampled ocean perch (Helicolenus barathri ) otoliths, collected at ∼400–500 m∼400–500 m in the Tasman Sea, to obtain measurements of View the MathML sourceΔC14 for those depths. We compared our ocean perch View the MathML sourceΔC14 series to published otolith-based marine surface water View the MathML sourceΔC14 values (Australasian snapper (Chrysophrys auratus) and nannygai (Centroberyx affinis)) and to published deep-water values (800–1000 m; orange roughy (Hoplostethus atlanticus )) from the southwest Pacific to establish a mid-water View the MathML sourceΔC14 series. The otolith bomb 14C results from these different depths were consistent with previous water mass results in the upper 1500 m of the southwest Pacific Ocean (e.g. World Ocean Circulation Experiment and Geochemical Ocean Sections Study). A comparison between the initial View the MathML sourceΔC14 bomb pulse rise at 400–500 m suggested a ventilation lag of 5 to 10 yr, whereas a comparison of the surface and depths of 800–1000 m detailed a 10 to 20 yr lag in the time history of radiocarbon invasion at this depth. Pre-bomb reservoir ages derived from otolith 14C located in Tasman Sea thermocline waters were ∼530 yr∼530 yr, while reservoir ages estimated for Tasman Antarctic intermediate water were ∼730 yr∼730 yr.
    Type: Article , PeerReviewed
    Format: text
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  • 2
    Publication Date: 2015-12-12
    Description: Background Anemia is very common in patients with human immunodeficiency virus (HIV)–associated tuberculosis, and hepcidin may be key in mediating this. We explored the relationship between blood hepcidin concentrations and anemia severity, mycobacterial burden and mortality in patients with HIV-associated tuberculosis. Methods Consecutive unselected HIV-infected adults in South Africa were systematically investigated for tuberculosis. Three groups were studied: 116 hospitalized inpatients with HIV infection and tuberculosis (hereafter, "hospitalized patients"), 58 ambulatory outpatients with HIV infection and newly diagnosed tuberculosis (hereafter, "ambulatory patients with tuberculosis"), and 58 ambulatory outpatients with HIV infection and without tuberculosis (hereafter, "ambulatory patients without tuberculosis"). Blood hepcidin concentrations were determined for all patients. Vital status at 3 months was determined, and independent predictors of mortality were identified. Results Median hepcidin concentrations were 38.8 ng/mL among hospitalized patients, 19.1 ng/mL among ambulatory patients with tuberculosis, and 5.9 ng/mL among ambulatory patients without tuberculosis ( P 〈 .001). In both groups with HIV-associated tuberculosis, hepcidin concentrations were strongly associated with greater anemia severity. Additionally, strong, graded associations were observed between hepcidin and composite indices of mycobacterial burden and dissemination. Patients dying within 3 months had significantly higher hepcidin concentrations, which independently predicted mortality. Conclusions High hepcidin concentrations were strongly associated with disseminated disease, anemia, and poor prognosis in patients with HIV-associated tuberculosis. Hepcidin may be a mechanistically important mediator underlying the high prevalence of severe anemia in these patients.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
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  • 3
    Publication Date: 2016-05-29
    Description: Background: International comparisons of perinatal health indicators are complicated by the heterogeneity of data sources on pregnancy, maternal and neonatal outcomes. Record linkage can extend the range of data items available and thus can improve the validity and quality of routine data. We sought to assess the extent to which data are linked routinely for perinatal health research and reporting. Methods: We conducted a systematic review of the literature by searching PubMed for perinatal health studies from 2001 to 2011 based on linkage of routine data (data collected continuously at various time intervals). We also surveyed European health monitoring professionals about use of linkage for national perinatal health surveillance. Results: 516 studies fit our inclusion criteria. Denmark, Finland, Norway and Sweden, the US and the UK contributed 76% of the publications; a further 29 countries contributed at least one publication. Most studies linked vital statistics, hospital records, medical birth registries and cohort data. Other sources were specific registers for: cancer (70), congenital anomalies (56), ART (19), census (19), health professionals (37), insurance (22) prescription (31), and level of education (18). Eighteen of 29 countries (62%) reported linking data for routine perinatal health monitoring. Conclusion: Research using linkage is concentrated in a few countries and is not widely practiced in Europe. Broader adoption of data linkage could yield substantial gains for perinatal health research and surveillance.
    Print ISSN: 1101-1262
    Electronic ISSN: 1464-360X
    Topics: Medicine
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  • 4
    Publication Date: 2016-05-25
    Description: Histone H3 methylation on Lys4 (H3K4me) is associated with active gene transcription in all eukaryotes. In Saccharomyces cerevisiae , Set1 is the sole lysine methyltransferase required for mono-, di-, and trimethylation of this site. Although H3K4me3 is linked to gene expression, whether H3K4 methylation regulates other cellular processes, such as mitosis, is less clear. Here we show that both Set1 and H3K4 mutants display a benomyl resistance phenotype that requires components of the spindle assembly checkpoint (SAC), including Bub3 and Mad2. These proteins inhibit Cdc20, an activator of the anaphase-promoting complex/cyclosome (APC/C). Mutations in Cdc20 that block Mad2 interactions suppress the benomyl resistance of both set1 and H3K4 mutant cells. Furthermore, the HORMA domain in Mad2 directly binds H3, identifying a new histone H3 "reader" motif. Mad2 undergoes a conformational change important for execution of the SAC. We found that the closed (active) conformation of both yeast and human Mad2 is capable of binding methylated H3K4, but, in contrast, the open (inactive) Mad2 conformation limits interaction with methylated H3. Collectively, our data indicate that interactions between Mad2 and H3K4 regulate resolution of the SAC by limiting closed Mad2 availability for Cdc20 inhibition.
    Print ISSN: 0890-9369
    Topics: Biology
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  • 5
    Publication Date: 2016-05-25
    Description: The effect of an increase in atmospheric aerosol concentrations on the distribution and radiative properties of Earth’s clouds is the most uncertain component of the overall global radiative forcing from preindustrial time. General circulation models (GCMs) are the tool for predicting future climate, but the treatment of aerosols, clouds, and...
    Keywords: Sackler Colloquium on Improving Our Fundamental Understanding of the Role of Aerosol&ndash ; Cloud Int
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2016-10-08
    Description: Learning disabilities have profound, long-lasting health sequelae. Affected children born over the course of 1 year in the United States of America generated an estimated lifetime cost of $51.2 billion. Results from some studies have suggested that autistic spectrum disorder may vary by season of birth, but there have been few studies in which investigators examined whether this is also true of other causes of learning disabilities. We undertook Scotland-wide record linkage of education (annual pupil census) and maternity (Scottish Morbidity Record 02) databases for 801,592 singleton children attending Scottish schools in 2006–2011. We modeled monthly rates using principal sine and cosine transformations of the month number and demonstrated cyclicity in the percentage of children with special educational needs. Rates were highest among children conceived in the first quarter of the year (January–March) and lowest among those conceived in the third (July–September) (8.9% vs 7.6%; P  〈 0.001). Seasonal variations were specific to autistic spectrum disorder, intellectual disabilities, and learning difficulties (e.g., dyslexia) and were absent for sensory or motor/physical impairments and mental, physical, or communication problems. Seasonality accounted for 11.4% (95% confidence interval: 9.0, 13.7) of all cases. Some biologically plausible causes of this variation, such as infection and maternal vitamin D levels, are potentially amendable to intervention.
    Print ISSN: 0002-9262
    Electronic ISSN: 1476-6256
    Topics: Medicine
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  • 7
    Publication Date: 2015-01-24
    Description: DNA polymerase zeta (pol ) is exceptionally important for controlling mutagenesis and genetic instability. REV3L comprises the catalytic subunit, while REV7 (MAD2L2) is considered an accessory subunit. However, it has not been established that the role of REV7 in DNA damage tolerance is necessarily connected with mammalian pol , and there is accumulating evidence that REV7 and REV3L have independent functions. Analysis of pol has been hampered by difficulties in expression of REV3L in mammalian cells, and lack of a functional complementation system. Here, we report that REV7 interacts with full-length REV3L in vivo and we identify a new conserved REV7 interaction site in human REV3L (residues 1993–2003), distinct from the known binding site (residues 1877–1887). Mutation of both REV7-binding sites eliminates the REV3L–REV7 interaction. In vivo complementation shows that both REV7-binding sites in REV3L are necessary for preventing spontaneous chromosome breaks and conferring resistance to UV radiation and cisplatin. This demonstrates a damage-specific function of REV7 in pol , in contrast to the distinct roles of REV3L and REV7 in primary cell viability and embryogenesis.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 8
    Publication Date: 2015-01-08
    Description: Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation Leukemia 29, 137 (January 2015). doi:10.1038/leu.2014.173 Authors: R B Walter, B Gyurkocza, B E Storer, C D Godwin, J M Pagel, S A Buckley, M L Sorror, B L Wood, R Storb, F R Appelbaum & B M Sandmaier
    Print ISSN: 0887-6924
    Electronic ISSN: 1476-5551
    Topics: Medicine
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  • 9
    Publication Date: 2015-09-11
    Description: Legionella organisms are environmental bacteria and accidental human pathogens that can cause severe pneumonia, termed Legionnaires' disease. These bacteria replicate within a pathogen-derived vacuole termed the Legionella -containing vacuole (LCV). Our understanding of the development and dynamics of this vacuole is based on extensive analysis of Legionella pneumophila . Here, we have characterized the Legionella longbeachae replicative vacuole ( longbeachae -LCV) and demonstrated that, despite important genomic differences, key features of the replicative LCV are comparable to those of the LCV of L. pneumophila ( pneumophila -LCV). We constructed a Dot/Icm-deficient strain by deleting dotB and demonstrated the inability of this mutant to replicate inside THP-1 cells. L. longbeachae does not enter THP-1 cells as efficiently as L. pneumophila , and this is reflected in the observation that translocation of BlaM-RalF LLO (where RalF LLO is the L. longbeachae homologue of RalF) into THP-1 cells by the L. longbeachae Dot/Icm system is less efficient than that by L. pneumophila . This difference is negated in A549 cells where L. longbeachae and L. pneumophila infect with similar entry dynamics. A β-lactamase assay was employed to demonstrate the translocation of a novel family of proteins, the R ab- l ike e ffector (Rle) proteins. Immunofluorescence analysis confirmed that these proteins enter the host cell during infection and display distinct subcellular localizations, with RleA and RleC present on the longbeachae -LCV. We observed that the host Rab GTPase, Rab1, and the v-SNARE Sec22b are also recruited to the longbeachae -LCV during the early stages of infection, coinciding with the LCV avoiding endocytic maturation. These studies further our understanding of the L. longbeachae replicative vacuole, highlighting phenotypic similarities to the vacuole of L. pneumophila as well as unique aspects of LCV biology.
    Print ISSN: 0019-9567
    Electronic ISSN: 1098-5522
    Topics: Medicine
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  • 10
    Publication Date: 2017-02-23
    Description: The Ediacaran skeletal tubular putative metazoan Cloudina occurs globally in carbonate settings, which both provided lithified substrates and minimized the cost of skeletonization. Habitat and substrate preferences and the relationship of Cloudina to other metazoans have not been fully documented, so we know little as to its ecological demands or community dynamics. In situ Cloudina from the Nama Group, Namibia (ca. 550–541 Ma), formed mutually attached reefs composed of successive assemblages in shallow, high-energy environments, and also communities attached to either stromatolites in storm-influenced deep inner-ramp settings or thin microbial mats in lower-energy habitats. Each assemblage shows statistically distinct tube diameter cohorts, but in sum, Cloudina shows an exponential frequency distribution of diameter size. In reefs, we document a periodicity of size variation, where mean, minimum, and maximum tube diameters vary together and show a systematic increase toward the top of each assemblage. We conclude that most Nama Group Cloudina represent one ecologically generalist taxon with highly variable size, that size was environmentally mediated, and that Cloudina could respond rapidly to periodic environmental changes. While Nama Group skeletal metazoans coexisted with soft-bodied biota, there was no apparent ecological interaction, as they were segregated into lithified carbonate and non-lithified clastic microbial mat communities, respectively. We infer that ecological flexibility allowed Cloudina to form varied communities that colonized diverse carbonate substrates under low levels of interspecific substrate competition. This is in notable contrast to the earliest Cambrian skeletal epibenthos that formed biodiverse reef communities with specialist niche occupancy.
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
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