Impacts of regional mixing on the temperature structure of the equatorial Pacific Ocean. Part 1: Vertically uniform vertical diffusion

AbstractWe investigate the sensitivity of numerical-model solutions to regional changes in vertical diffusion. Specifically, we vary the background diffusion coefficient, κb, within spatially distinct subregions of the tropical Pacific, assess the impacts of those changes, and diagnose the processes that account for them.Solutions respond to a diffusion anomaly, δκb, in three ways. Initially, there is a fast response (several months), due to the interaction of rapidly-propagating, barotropic and gravity waves with eddies and other mesoscale features. It is followed by a local response (roughly one year), the initial growth and spatial pattern of which can be explained by one-dimensional (vertical) diffusion. At this stage, temperature and salinity anomalies are generated that are either associated with a change in density (“dynamical” anomalies) or without one (“spiciness” anomalies). In a final adjustment stage, the dynamical and spiciness anomalies spread to remote regions by radiation of Rossby and Kelvin waves and by advection, respectively.In near-equilibrium solutions, dynamical anomalies are generally much larger in the latitude band of the forcing, but the impact of off-equatorial forcing by δκb on the equatorial temperature structure is still significant. Spiciness anomalies spread equatorward within the pycnocline, where they are carried to the equator as part of the subsurface branch of the Pacific Subtropical Cells, and spiciness also extends to the equator via western-boundary currents. Forcing near and at the equator generates strong dynamical anomalies, and sometimes additional spiciness anomalies, at pycnocline depths. The total response of the equatorial temperature structure to δκb in various regions depends on the strength and spatial pattern of the generation of each signal within the forcing region as well as on the processes of its spreading to the equator

Distinctive dendritic cell subsets expressing factor XIIIa, CD1a, CD1b and CD1c in mycosis fungoides and psoriasis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73825/1/j.1600-0560.1995.tb00742.x.pd

Measuring atopic eczema symptoms in clinical practice: The first consensus statement from the Harmonising Outcome Measures for Eczema in clinical practice initiative

Background: Measuring patient-centered outcomes in clinical practice is valuable for monitoring patients and advancing real-world research. A new initiative from the Harmonising Outcome Measures for Eczema (HOME) group aims to recommend what might be recorded for atopic eczema patients in routine clinical care. Objectives: Prioritize outcome domains to measure atopic eczema in clinical practice and select valid and practical outcome measurement instruments for the highest-priority domain. Methods: An online survey of HOME members identified and ranked 21 possible health domains. Suitable instruments were then selected for the top-prioritized domain at the HOME VI meeting, using established consensus processes informed by systematic reviews of instrument quality. Results: Patient-reported symptoms was the top-prioritized domain. In accordance with psychometric properties and feasibility, there was consensus that the recommended instruments to measure atopic eczema symptoms in clinical practice are the POEM, the PO-SCORAD index, or both. The numeric rating scale for itch received support pending definition and validation in atopic eczema. Conclusion: Following the first step of the HOME Clinical Practice initiative, we endorse using the POEM, the PO-SCORAD index, or both for measuring atopic eczema symptoms in clinical practice. Additional high-priority domains for clinical practice will be assessed at subsequent HOME meetings

BMP4 induction of trophoblast from mouse embryonic stem cells in defined culture conditions on laminin

Because mouse embryonic stem cells (mESCs) do not contribute to the formation of extraembryonic placenta when they are injected into blastocysts, it is believed that mESCs do not differentiate into trophoblast whereas human embryonic stem cells (hESCs) can express trophoblast markers when exposed to bone morphogenetic protein 4 (BMP4) in vitro. To test whether mESCs have the potential to differentiate into trophoblast, we assessed the effect of BMP4 on mESCs in a defined monolayer culture condition. The expression of trophoblast-specific transcription factors such as Cdx2, Dlx3, Esx1, Gata3, Hand1, Mash2, and Plx1 was specifically upregulated in the BMP4-treated differentiated cells, and these cells expressed trophoblast markers. These results suggest that BMP4 treatment in defined culture conditions enabled mESCs to differentiate into trophoblast. This differentiation was inhibited by serum or leukemia inhibitory factor, which are generally used for mESC culture. In addition, we studied the mechanism underlying BMP4-directed mESC differentiation into trophoblast. Our results showed that BMP4 activates the Smad pathway in mESCs inducing Cdx2 expression, which plays a crucial role in trophoblast differentiation, through the binding of Smad protein to the Cdx2 genomic enhancer sequence. Our findings imply that there is a common molecular mechanism underlying hESC and mESC differentiation into trophoblast

Variants of C-C Motif Chemokine 22 (CCL22) Are Associated with Susceptibility to Atopic Dermatitis: Case-Control Studies

Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1st population, 916 cases and 1,032 controls; 2nd population 1,034 cases and 1,004 controls). After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10−6; OR, 0.74; 95% CI, 0.65–0.85). Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD

Human Fetal Liver Stromal Cells That Overexpress bFGF Support Growth and Maintenance of Human Embryonic Stem Cells

In guiding hES cell technology toward the clinic, one key issue to be addressed is to culture and maintain hES cells much more safely and economically in large scale. In order to avoid using mouse embryonic fibroblasts (MEFs) we isolated human fetal liver stromal cells (hFLSCs) from 14 weeks human fetal liver as new human feeder cells. hFLSCs feeders could maintain hES cells for 15 passages (about 100 days). Basic fibroblast growth factor (bFGF) is known to play an important role in promoting self-renewal of human embryonic stem (hES) cells. So, we established transgenic hFLSCs that stably express bFGF by lentiviral vectors. These transgenic human feeder cells — bFGF-hFLSCs maintained the properties of H9 hES cells without supplementing with any exogenous growth factors. H9 hES cells culturing under these conditions maintained all hES cell features after prolonged culture, including the developmental potential to differentiate into representative tissues of all three embryonic germ layers, unlimited and undifferentiated proliferative ability, and maintenance of normal karyotype. Our results demonstrated that bFGF-hFLSCs feeder cells were central to establishing the signaling network among bFGF, insulin-like growth factor 2 (IGF-2), and transforming growth factor β (TGF-β), thereby providing the framework in which hES cells were instructed to self-renew or to differentiate. We also found that the conditioned medium of bFGF-hFLSCs could maintain the H9 hES cells under feeder-free conditions without supplementing with bFGF. Taken together, bFGF-hFLSCs had great potential as feeders for maintaining pluripotent hES cell lines more safely and economically

Progress in understanding of Indian Ocean circulation, variability, air-sea exchange and impacts on biogeochemistry

Over the past decade, our understanding of the Indian Ocean has advanced through concerted efforts toward measuring the ocean circulation and air–sea exchanges, detecting changes in water masses, and linking physical processes to ecologically important variables. New circulation pathways and mechanisms have been discovered that control atmospheric and oceanic mean state and variability. This review brings together new understanding of the ocean–atmosphere system in the Indian Ocean since the last comprehensive review, describing the Indian Ocean circulation patterns, air–sea interactions, and climate variability. Coordinated international focus on the Indian Ocean has motivated the application of new technologies to deliver higher-resolution observations and models of Indian Ocean processes. As a result we are discovering the importance of small-scale processes in setting the large-scale gradients and circulation, interactions between physical and biogeochemical processes, interactions between boundary currents and the interior, and interactions between the surface and the deep ocean. A newly discovered regional climate mode in the southeast Indian Ocean, the Ningaloo Niño, has instigated more regional air–sea coupling and marine heatwave research in the global oceans. In the last decade, we have seen rapid warming of the Indian Ocean overlaid with extremes in the form of marine heatwaves. These events have motivated studies that have delivered new insight into the variability in ocean heat content and exchanges in the Indian Ocean and have highlighted the critical role of the Indian Ocean as a clearing house for anthropogenic heat. This synthesis paper reviews the advances in these areas in the last decade