Impact of recently upwelled water on productivity investigated using in situ and incubation-based methods in Monterey Bay

Author Posting. © American Geophysical Union, 2017. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 122 (2017): 1901–1926, doi:10.1002/2016JC012306.Photosynthetic conversion of inline image to organic carbon and the transport of this carbon from the surface to the deep ocean is an important regulator of atmospheric inline image. To understand the controls on carbon fluxes in a productive region impacted by upwelling, we measured biological productivity via multiple methods during a cruise in Monterey Bay, California. We quantified net community production and gross primary production from measurements of inline image/Ar and inline image triple isotopes ( inline image), respectively. We simultaneously conducted incubations measuring the uptake of 14C, inline image, and inline image, and nitrification, and deployed sediment traps. At the start of the cruise (Phase 1) the carbon cycle was at steady state and the estimated net community production was 35(10) and 35(8) mmol C m−2 d−1 from inline image/Ar and 15N incubations, respectively, a remarkably good agreement. During Phase 1, net primary production was 96(27) mmol C m−2 d−1 from C uptake, and gross primary production was 209(17) mmol C m−2 d−1 from inline image. Later in the cruise (Phase 2), recently upwelled water with higher nutrient concentrations entered the study area, causing 14C and inline image uptake to increase substantially. Continuous inline image/Ar measurements revealed submesoscale variability in water mass structure and likely productivity in Phase 2 that was not evident from the incubations. These data demonstrate that inline image/Ar and inline image incubation-based NCP estimates can give equivalent results in an N-limited, coastal system, when the nonsteady state inline image fluxes are negligible or can be quantified.Funding for this work was provided by NSF awards OCE-1060840 to R.H.R. Stanley, OCE-1129644 to D.P. Nicholson, OCE-1357042 to F.P. Chavez, NASA award NNX14AI06G to M.R. Fewings, the David and Lucile Packard Foundation through their generous annual donation to the Monterey Bay Aquarium Research Institute, an Ocean Ventures Fund award from the WHOI Academic Programs Office to CC Manning, and graduate scholarships from NSERC and CMOS to CC Manning.2017-09-1

Design management: changing roles of the professions

This paper sets out to explore how recent changes in procurement in construction have affected the roles that professions play in the design process. It discusses how professions that traditionally took the role of design manager now find themselves participating within previously unforeseen contexts, working in multidisciplinary teams led by contractors and with changed responsibilities at the design stage. Supply chain members who were not previously involved during the early project phases are being engaged at the earliest phases of the project life cycle and even taking leadership roles while designers sometimes work as supply chain partners. A study of design in construction and other sectors shows that in dealing with design management issues it is critical to deepen appreciation for the unique characteristics of design and the design process. The paper argues that contractors and designers taking on design management roles in a dynamic industry seeking to explore best practice and innovative approaches to procurement and in the delivery of projects need to acquire new skills, management education and develop the necessary qualities

Along-shelf current variability on the Catalan inner-shelf (NW Mediterranean)

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 117 (2012): C09027, doi:10.1029/2012JC008182.We examine the circulation over the inner-shelf of the Catalan Sea using observations of currents obtained from three Acoustic Doppler Current Profilers (two at 24 m and one at 50 m) during March–April 2011. The along-shelf current fluctuations during that period are mainly controlled by local wind stress on short time scales and by remote pressure gradients on synoptic time scales. Different forcing mechanisms are involved in the along-shelf momentum balance. During storm conditions, wind stress, sea level gradients and the nonlinear terms dominate the balance. During weak wind conditions, the momentum balance is controlled by the pressure gradient, while during periods of moderate wind in the presence of considerable stratification, the balance is established between the Coriolis and wind stress terms. Vertical variations of velocity are affected by the strong observed density gradient. The increased vertical shear is accompanied by the development of stratified conditions due to local heating when the wind is not able to counteract (and break) stratification. The occasional influence of the Besòs River plume is observed in time scales of hours to days in a limited area in near the city of Barcelona. The area affected by the plume depends on the vertical extent of the fresher layer, the fast river discharge peak, and the relaxation of cross-shore velocities after northeast storm events. This contribution provides a first interpretation of the inner-shelf dynamics in the Catalan Sea.The research leading to these results has received funding fromthe European Community’s Seventh Framework Programme (FP7/2007/2013) under grant agreement 242284 (Field_ac project).2013-03-2

Planktonic foraminiferal assemblages reflect warming during two recent mid-latitude marine heatwaves

Under future climate scenarios, ocean temperatures that are presently extreme and qualify as marine heatwaves (MHW) are forecasted to increase in frequency and intensity, but little is known about the impact of these events on one of the most common paleoproxies, planktonic foraminifera. Planktonic foraminifera are globally ubiquitous, shelled marine protists. Their abundances and geochemistry vary with ocean conditions and fossil specimens are commonly used to reconstruct ancient ocean conditions. Planktonic foraminiferal assemblages are known to vary globally with sea surface temperature, primary productivity, and other hydrographic conditions, but have not been studied in the context of mid-latitude MHWs. For this study, the community composition and abundance of planktonic foraminifera were quantified for 2010-2019 along the Newport Hydrographic Line, a long-term monitoring transect at 44.6°N in the Northern California Current (NCC). Samples were obtained from archived plankton tows spanning 46 to 370 km offshore during annual autumn (August – October) cruises. Two MHWs impacted the region during this timeframe: the first during 2014-2016 and a second, shorter duration MHW in 2019. During the 2014-2016 MHW, warm water subtropical and tropical foraminifera species were more prevalent than the typical polar, subpolar, and transitional species common to this region. Cold water species were abundant again after the first MHW dissipated in late 2016. During the second, shorter-duration MHW in 2019, the assemblage consisted of a warm water assemblage but did not include tropical species. The foraminiferal assemblage variability correlated with changes in temperature and salinity in the upper 100 meters and was not correlated with distance offshore or upwelling. These results suggest that fossil foraminiferal assemblages from deep sea sediment cores may provide insight into the magnitude and frequency of past MHWs

Experiences of domestic violence prevention interventions and gender equality promotion work: a qualitative study of Nirdhar Groups in rural India [version 1; peer review: awaiting peer review]

Domestic violence and abuse (DVA) against women in India is a serious concern. To address this, community-based interventions to facilitate sustained change at local levels have been implemented in 37 villages by the Halo Medical Foundation (an NGO working in the Maharashtra state of India). This qualitative study of community led alliances (known as Nirdhar Groups) evaluates the experiences of these ‘community citizen groups’. Participants from 12 villages from the project area participated in qualitative focus group discussions. Nirdhar Groups used local interventions to address priorities such as safe and equal access to education and healthcare. They offered education to address financial oppression and used community pressure and ‘Responsible Couples’ as mechanisms for change, to instil ‘fairness, gender equality, kind and compassionate community values’ and a variety of techniques to reduce DVA. The drivers for change included role modelling, empowerment of women in communities and a focus on changing cultural practices for present and future generations. This paper reveals how local interventions empower communities to address gender disparities and DV

Physiologically based pharmacokinetic modeling of arterial – antecubital vein concentration difference

BACKGROUND: Modeling of pharmacokinetic parameters and pharmacodynamic actions requires knowledge of the arterial blood concentration. In most cases, experimental measurements are only available for a peripheral vein (usually antecubital) whose concentration may differ significantly from both arterial and central vein concentration. METHODS: A physiologically based pharmacokinetic (PBPK) model for the tissues drained by the antecubital vein (referred to as "arm") is developed. It is assumed that the "arm" is composed of tissues with identical properties (partition coefficient, blood flow/gm) as the whole body tissues plus a new "tissue" representing skin arteriovenous shunts. The antecubital vein concentration depends on the following parameters: the fraction of "arm" blood flow contributed by muscle, skin, adipose, connective tissue and arteriovenous shunts, and the flow per gram of the arteriovenous shunt. The value of these parameters was investigated using simultaneous experimental measurements of arterial and antecubital concentrations for eight solutes: ethanol, thiopental, (99)Tc(m)-diethylene triamine pentaacetate (DTPA), ketamine, D(2)O, acetone, methylene chloride and toluene. A new procedure is described that can be used to determine the arterial concentration for an arbitrary solute by deconvolution of the antecubital concentration. These procedures are implemented in PKQuest, a general PBPK program that is freely distributed . RESULTS: One set of "standard arm" parameters provides an adequate description of the arterial/antecubital vein concentration for ethanol, DTPA, thiopental and ketamine. A significantly different set of "arm" parameters was required to describe the data for D(2)O, acetone, methylene chloride and toluene – probably because the "arm" is in a different physiological state. CONCLUSIONS: Using the set of "standard arm" parameters, the antecubital vein concentration can be used to determine the whole body PBPK model parameters for an arbitrary solute without any additional adjustable parameters. Also, the antecubital vein concentration can be used to estimate the arterial concentration for an arbitrary input for solutes for which no arterial concentration data is available

Germline pathogenic variants in PALB2 and other cancer-predisposing genes in families with hereditary diffuse gastric cancer without CDH1 mutation: a whole-exome sequencing study.

BACKGROUND: Germline pathogenic variants in the E-cadherin gene (CDH1) are strongly associated with the development of hereditary diffuse gastric cancer. There is a paucity of data to guide risk assessment and management of families with hereditary diffuse gastric cancer that do not carry a CDH1 pathogenic variant, making it difficult to make informed decisions about surveillance and risk-reducing surgery. We aimed to identify new candidate genes associated with predisposition to hereditary diffuse gastric cancer in affected families without pathogenic CDH1 variants. METHODS: We did whole-exome sequencing on DNA extracted from the blood of 39 individuals (28 individuals diagnosed with hereditary diffuse gastric cancer and 11 unaffected first-degree relatives) in 22 families without pathogenic CDH1 variants. Genes with loss-of-function variants were prioritised using gene-interaction analysis to identify clusters of genes that could be involved in predisposition to hereditary diffuse gastric cancer. FINDINGS: Protein-affecting germline variants were identified in probands from six families with hereditary diffuse gastric cancer; variants were found in genes known to predispose to cancer and in lesser-studied DNA repair genes. A frameshift deletion in PALB2 was found in one member of a family with a history of gastric and breast cancer. Two different MSH2 variants were identified in two unrelated affected individuals, including one frameshift insertion and one previously described start-codon loss. One family had a unique combination of variants in the DNA repair genes ATR and NBN. Two variants in the DNA repair gene RECQL5 were identified in two unrelated families: one missense variant and a splice-acceptor variant. INTERPRETATION: The results of this study suggest a role for the known cancer predisposition gene PALB2 in families with hereditary diffuse gastric cancer and no detected pathogenic CDH1 variants. We also identified new candidate genes associated with disease risk in these families. FUNDING: UK Medical Research Council (Sackler programme), European Research Council under the European Union's Seventh Framework Programme (2007-13), National Institute for Health Research Cambridge Biomedical Research Centre, Experimental Cancer Medicine Centres, and Cancer Research UK

Characterization of the macrophage transcriptome in glomerulonephritis-susceptible and -resistant rat strains

Crescentic glomerulonephritis (CRGN) is a major cause of rapidly progressive renal failure for which the underlying genetic basis is unknown. WKY rats show marked susceptibility to CRGN, while Lewis rats are resistant. Glomerular injury and crescent formation are macrophage-dependent and mainly explained by seven quantitative trait loci (Crgn1-7). Here, we used microarray analysis in basal and lipopolysaccharide (LPS)-stimulated macrophages to identify genes that reside on pathways predisposing WKY rats to CRGN. We detected 97 novel positional candidates for the uncharacterised Crgn3-7. We identified 10 additional secondary effector genes with profound differences in expression between the two strains (>5-fold change, <1% False Discovery Rate) for basal and LPS-stimulated macrophages. Moreover, we identified 8 genes with differentially expressed alternatively spliced isoforms, by using an in depth analysis at probe-level that allowed us to discard false positives due to polymorphisms between the two rat strains. Pathway analysis identified several common linked pathways, enriched for differentially expressed genes, which affect macrophage activation. In summary, our results identify distinct macrophage transcriptome profiles between two rat strains that differ in susceptibility to glomerulonephritis, provide novel positional candidates for Crgn3-7, and define groups of genes that play a significant role in differential regulation of macrophage activity

Genome-wide Association Study of Response to Methotrexate in Early Rheumatoid Arthritis Patients

Methotrexate (MTX) monotherapy is a common first treatment for rheumatoid arthritis (RA), but many patients do not respond adequately. In order to identify genetic predictors of response, we have combined data from two consortia to carry out a genome-wide study of response to MTX in 1424 early RA patients of European ancestry. Clinical endpoints were change from baseline to 6 months after starting treatment in swollen 28-joint count, tender 28-joint count, C-reactive protein and the overall 3-component disease activity score (DAS28). No single nucleotide polymorphism (SNP) reached genome-wide statistical significance for any outcome measure. The strongest evidence for association was with rs168201 in NRG3 (p = 10‾⁷ for change in DAS28). Some support was also seen for association with ZMIZ1, previously highlighted in a study of response to MTX in juvenile idiopathic arthritis. Follow-up in two smaller cohorts of 429 and 177 RA patients did not support these findings, although these cohorts were more heterogeneous

Alternative splicing and transcriptome profiling of experimental autoimmune encephalomyelitis using genome-wide exon arrays

BACKGROUND: Multiple Sclerosis (MS) is a chronic inflammatory disease causing demyelination and nerve loss in the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is widely used to investigate complex pathogenic mechanisms. Transcriptional control through isoform selection and mRNA levels determines pathway activation and ultimately susceptibility to disease. METHODOLOGY/PRINCIPAL FINDINGS: We have studied the role of alternative splicing and differential expression in lymph node cells from EAE-susceptible Dark Agouti (DA) and EAE-resistant Piebald Virol Glaxo.AV1 (PVG) inbred rat strains using Affymetrix Gene Chip Rat Exon 1.0 ST Arrays. Comparing the two strains, we identified 11 differentially spliced and 206 differentially expressed genes at day 7 post-immunization, as well as 9 differentially spliced and 144 differentially expressed genes upon autoantigen re-stimulation. Functional clustering and pathway analysis implicate genes for glycosylation, lymphocyte activation, potassium channel activity and cellular differentiation in EAE susceptibility. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that alternative splicing occurs during complex disease and may govern EAE susceptibility. Additionally, transcriptome analysis not only identified previously defined EAE pathways regulating the immune system, but also novel mechanisms. Furthermore, several identified genes overlap known quantitative trait loci, providing novel causative candidate targets governing EAE