Wave attenuation at a salt marsh margin: A case study of an exposed coast on the Yangtze estuary

To quantify wave attenuation by (introduced) Spartina alterniflora vegetation at an exposed macrotidal coast in the Yangtze Estuary, China, wave parameters and water depth were measured during 13 consecutive tides at nine locations ranging from 10 m seaward to 50 m landward of the low marsh edge. During this period, the incident wave height ranged from <0.1 to 1.5 m, the maximum of which is much higher than observed in other marsh areas around the world. Our measurements and calculations showed that the wave attenuation rate per unit distance was 1 to 2 magnitudes higher over the marsh than over an adjacent mudflat. Although the elevation gradient of the marsh margin was significantly higher than that of the adjacent mudflat, more than 80% of wave attenuation was ascribed to the presence of vegetation, suggesting that shoaling effects were of minor importance. On average, waves reaching the marsh were eliminated over a distance of similar to 80 m, although a marsh distance of >= 100 m was needed before the maximum height waves were fully attenuated during high tides. These attenuation distances were longer than those previously found in American salt marshes, mainly due to the macrotidal and exposed conditions at the present site. The ratio of water depth to plant height showed an inverse correlation with wave attenuation rate, indicating that plant height is a crucial factor determining the efficiency of wave attenuation. Consequently, the tall shoots of the introduced S. alterniflora makes this species much more efficient at attenuating waves than the shorter, native pioneer species in the Yangtze Estuary, and should therefore be considered as a factor in coastal management during the present era of sea-level rise and global change. We also found that wave attenuation across the salt marsh can be predicted using published models when a suitable coefficient is incorporated to account for drag, which varies in place and time due to differences in plant characteristics and abiotic conditions (i.e., bed gradient, initial water depth, and wave action).

Erosion and Accretion on a Mudflat: The Importance of Very Shallow-Water Effects

Understanding erosion and accretion dynamics during an entire tidal cycle is important for assessing their impacts on the habitats of biological communities and the long‐term morphological evolution of intertidal mudflats. However, previous studies often omitted erosion and accretion during very shallow‐water stages (VSWS, water depths 0.2 m (i.e., probe submerged) are considered. These findings suggest that the magnitude of bed‐level changes during VSWS should not be neglected when modeling morphodynamic processes. Our results are useful in understanding the mechanisms of micro‐topography formation and destruction that often occur at VSWS, and also improve our understanding and modeling ability of coastal morphological changes

Tracing magnetism and pairing in FeTe-based systems

In order to examine the interplay between magnetism and superconductivity, we monitor the non- superconducting chalcogenide FeTe and follow its transitions under insertion of oxygen, doping with Se and vacancies of Fe using spin-polarized band structure methods (LSDA with GGA) starting from the collinear and bicollinear magnetic arrangements. We use a supercell of Fe8Te8 as our starting point so that it can capture local changes in magnetic moments. The calculated values of magnetic moments agree well with available experimental data while oxygen insertions lead to significant changes in the bicollinear or collinear magnetic moments. The total energies of these systems indicate that the collinear-derived structure is the more favorable one prior to a possible superconducting transition. Using a 8-site Betts-cluster-based lattice and the Hubbard model, we show why this structure favors electron or hole pairing and provides clues to a common understanding of charge and spin pairing in the cuprates, pnictides and chalcogenides

Responsiveness differences in outcome instruments after revision hip arthroplasty: What are the implications?

Responsiveness to change is an important psychometric property of an outcome instrument. Assessment of health-related quality of life (HRQoL) is critical to outcome assessment after total joint replacement, a surgery aimed at improving pain, function and HRQoL of the patients undergoing these procedures. In a recent study, Shi et al. examined the responsiveness to change of various subscales of two instruments, physician-administered Harris Hip Score and patient self-administered Short Form-36 (SF-36), 6 months after revision total hip arthroplasty. The responsiveness statistics for both scales were reasonable, higher for Harris Hip Score than SF-36. This is the first study to examine responsiveness of these instruments in revision THA patients in a systematic fashion

Patterns of primary care and mortality among patients with schizophrenia or diabetes: a cluster analysis approach to the retrospective study of healthcare utilization

Abstract Background Patients with schizophrenia have difficulty managing their medical healthcare needs, possibly resulting in delayed treatment and poor outcomes. We analyzed whether patients reduced primary care use over time, differentially by diagnosis with schizophrenia, diabetes, or both schizophrenia and diabetes. We also assessed whether such patterns of primary care use were a significant predictor of mortality over a 4-year period. Methods The Veterans Healthcare Administration (VA) is the largest integrated healthcare system in the United States. Administrative extracts of the VA's all-electronic medical records were studied. Patients over age 50 and diagnosed with schizophrenia in 2002 were age-matched 1:4 to diabetes patients. All patients were followed through 2005. Cluster analysis explored trajectories of primary care use. Proportional hazards regression modelled the impact of these primary care utilization trajectories on survival, controlling for demographic and clinical covariates. Results Patients comprised three diagnostic groups: diabetes only (n = 188,332), schizophrenia only (n = 40,109), and schizophrenia with diabetes (Scz-DM, n = 13,025). Cluster analysis revealed four distinct trajectories of primary care use: consistent over time, increasing over time, high and decreasing, low and decreasing. Patients with schizophrenia only were likely to have low-decreasing use (73% schizophrenia-only vs 54% Scz-DM vs 52% diabetes). Increasing use was least common among schizophrenia patients (4% vs 8% Scz-DM vs 7% diabetes) and was associated with improved survival. Low-decreasing primary care, compared to consistent use, was associated with shorter survival controlling for demographics and case-mix. The observational study was limited by reliance on administrative data. Conclusion Regular primary care and high levels of primary care were associated with better survival for patients with chronic illness, whether psychiatric or medical. For schizophrenia patients, with or without comorbid diabetes, primary care offers a survival benefit, suggesting that innovations in treatment retention targeting at-risk groups can offer significant promise of improving outcomes.http://deepblue.lib.umich.edu/bitstream/2027.42/78274/1/1472-6963-9-127.xmlhttp://deepblue.lib.umich.edu/bitstream/2027.42/78274/2/1472-6963-9-127.pdfPeer Reviewe

Roles for Treg expansion and HMGB1 signaling through the TLR1-2-6 axis in determining the magnitude of the antigen-specific immune response to MVA85A

© 2013 Matsumiya et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedA better understanding of the relationships between vaccine, immunogenicity and protection from disease would greatly facilitate vaccine development. Modified vaccinia virus Ankara expressing antigen 85A (MVA85A) is a novel tuberculosis vaccine candidate designed to enhance responses induced by BCG. Antigen-specific interferon-γ (IFN-γ) production is greatly enhanced by MVA85A, however the variability between healthy individuals is extensive. In this study we have sought to characterize the early changes in gene expression in humans following vaccination with MVA85A and relate these to long-term immunogenicity. Two days post-vaccination, MVA85A induces a strong interferon and inflammatory response. Separating volunteers into high and low responders on the basis of T cell responses to 85A peptides measured during the trial, an expansion of circulating CD4+ CD25+ Foxp3+ cells is seen in low but not high responders. Additionally, high levels of Toll-like Receptor (TLR) 1 on day of vaccination are associated with an increased response to antigen 85A. In a classification model, combined expression levels of TLR1, TICAM2 and CD14 on day of vaccination and CTLA4 and IL2Rα two days post-vaccination can classify high and low responders with over 80% accuracy. Furthermore, administering MVA85A in mice with anti-TLR2 antibodies may abrogate high responses, and neutralising antibodies to TLRs 1, 2 or 6 or HMGB1 decrease CXCL2 production during in vitro stimulation with MVA85A. HMGB1 is released into the supernatant following atimulation with MVA85A and we propose this signal may be the trigger activating the TLR pathway. This study suggests an important role for an endogenous ligand in innate sensing of MVA and demonstrates the importance of pattern recognition receptors and regulatory T cell responses in determining the magnitude of the antigen specific immune response to vaccination with MVA85A in humans.This work was funded by the Wellcome Trust. MM has a Wellcome Trust PhD studentship and HM is a Wellcome Trust Senior Fello

Characterization of the Major Histocompatibility Complex Class II Genes in Miiuy Croaker

Major histocompatibility complex (MHC) has a central role in the adaptive immune system by presenting foreign peptide to the T-cell receptor. In order to study the molecular function and genomic characteristic of class II genes in teleost, the full lengths of MHC class IIA and IIB cDNA and genomic sequence were cloned from miiuy croaker (Miichthys miiuy). As in other teleost, four exons and three introns were identified in miiuy croaker class IIA gene; but the difference is that six exons and five introns were identified in the miiuy croaker class IIB gene. The deduced amino acid sequence of class IIA and class IIB had 26.3–85.7% and 11.0–88.8% identity with those of mammal and teleost, respectively. Real-time quantitative RT-PCR demonstrated that the MHC class IIA and IIB were ubiquitously expressed in ten normal tissues; expression levels of MHC genes were found first upregulated and then downregulated, and finally by a recovery to normal level throughout the pathogenic bacteria infection process. In addition, we report on the underlying mechanism that maintains sequences diversity among many fish species. A series of site-model tests implemented in the CODEML program revealed that positive Darwinian selection is likely the cause of the molecular evolution in the fish MHC class II genes

Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols

The chirality, or ‘handedness’, of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation. Despite many advances in asymmetric synthesis, developing general and practical strategies for obtaining all possible stereoisomers of an organic compound that has multiple contiguous stereocentres remains a challenge3. Here, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, we synthesized these amino-alcohol products using sequential, copper-hydride-catalysed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino-alcohol products, which contain up to three contiguous stereocentres. We leveraged catalyst control and stereospecificity simultaneously to attain exceptional control of the product stereochemistry. Beyond the immediate utility of this protocol, our strategy could inspire the development of methods that provide complete sets of stereoisomers for other valuable synthetic targets.National Institutes of Health (U.S.) (Grant GM-58160

Identification of chemokine receptors as potential modulators of endocrine resistance in oestrogen receptor–positive breast cancers

Introduction Endocrine therapies target oestrogenic stimulation of breast cancer (BC) growth, but resistance remains problematic. Our aims in this study were (1) to identify genes most strongly associated with resistance to endocrine therapy by intersecting global gene transcription data from patients treated presurgically with the aromatase inhibitor anastrazole with those from MCF7 cells adapted to long-term oestrogen deprivation (LTED) (2) to assess the clinical value of selected genes in public clinical data sets and (3) to determine the impact of targeting these genes with novel agents. Methods Gene expression and Ki67 data were available from 69 postmenopausal women with oestrogen receptor–positive (ER+) early BC, at baseline and 2 weeks after anastrazole treatment, and from cell lines adapted to LTED. The functional consequences of target genes on proliferation, ER-mediated transcription and downstream cell signalling were assessed. Results By intersecting genes predictive of a poor change in Ki67 with those upregulated in LTED cells, we identified 32 genes strongly correlated with poor antiproliferative response that were associated with inflammation and/or immunity. In a panel of LTED cell lines, C-X-C chemokine receptor type 7 (CXCR7) and CXCR4 were upregulated compared to their wild types (wt), and CXCR7, but not CXCR4, was associated with reduced relapse-free survival in patients with ER+ BC. The CXCR4 small interfering RNA variant (siCXCR4) had no specific effect on the proliferation of wt-SUM44, wt-MCF7 and their LTED derivatives. In contrast, siCXCR7, as well as CCX733, a CXCR7 antagonist, specifically suppressed the proliferation of MCF7-LTED cells. siCXCR7 suppressed proteins associated with G1/S transition and inhibited ER transactivation in MCF7-LTED, but not wt-MCF7, by impeding association between ER and proline-, glutamic acid– and leucine-rich protein 1, an ER coactivator. Conclusions These data highlight CXCR7 as a potential therapeutic target warranting clinical investigation in endocrine-resistant BC

Hepatitis C virus cell-cell transmission and resistance to direct-acting antiviral agents

Hepatitis C virus (HCV) is transmitted between hepatocytes via classical cell entry but also uses direct cell-cell transfer to infect neighboring hepatocytes. Viral cell-cell transmission has been shown to play an important role in viral persistence allowing evasion from neutralizing antibodies. In contrast, the role of HCV cell-cell transmission for antiviral resistance is unknown. Aiming to address this question we investigated the phenotype of HCV strains exhibiting resistance to direct-acting antivirals (DAAs) in state-of-the-art model systems for cell-cell transmission and spread. Using HCV genotype 2 as a model virus, we show that cell-cell transmission is the main route of viral spread of DAA-resistant HCV. Cell-cell transmission of DAA-resistant viruses results in viral persistence and thus hampers viral eradication. We also show that blocking cell-cell transmission using host-targeting entry inhibitors (HTEIs) was highly effective in inhibiting viral dissemination of resistant genotype 2 viruses. Combining HTEIs with DAAs prevented antiviral resistance and led to rapid elimination of the virus in cell culture model. In conclusion, our work provides evidence that cell-cell transmission plays an important role in dissemination and maintenance of resistant variants in cell culture models. Blocking virus cell-cell transmission prevents emergence of drug resistance in persistent viral infection including resistance to HCV DAAs