The role of cyclic climatic regimes and riparian vegetation: a qualitative and quantitative study into the cause of river bank slope instability and channel widening on the Macdonald River, New South Wales.

Numerous case studies have demonstrated the catastrophic nature of channel change experienced on the Macdonald River, a tributary of the Hawkesbury-Nepean River, New South Wales. However, there is an absence of studies that clearly state how and why the channel changed as dramatically as it did. As a consequence, the magnitude of, and ultimate controls on the changes to the Macdonald River’s form and processes are not fully appreciated. In this study, a comparison is undertaken on the three existing river morphology perspectives with respect to the Macdonald River. The Warner and Erskine Perspective states the sole importance of the cyclic hydro-climatic conditions of the FDR and DDRs on river morphology. The Brierely and co-workers Perspective states the sole importance of anthropogenic influence in the catchment and on the banks on river morphology. The Intermediate Perspective of Hubble and co-workers considers both existing and conflicting perspectives and states the importance of both cyclic climatic regimes and anthropogenic activity in the catchment and particularly on the river banks, in determining river morphology. Resultantly, a selection of Hubble and co-workers Perspective is made to classify the Macdonald River’s morphology. It is clear, from the analysis of historical aerial photographs, archival sketches, photographs and historical documentation, that riparian vegetation was absent from the banks of the Macdonald River from 1941 as a result of land-clearing practices from the early 19th Century. The banks of the Macdonald River would not have experienced this ‘catastrophic’ channel change between 1949 and 1955 had riparian vegetation remained on the banks. Riparian vegetation has been found to increase the soil-shear strength and hence the stability of river bank slopes, in particularly on the Upper Nepean and the Macdonald Rivers in New South Wales, where vulnerable sands to silty-sands predominate the bank material. This has been further proved with geochemical bank stability modeling

Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells

Ageing is a broad cellular process, largely affecting the immune system, especially T-lymphocytes. Additionally to immunosenescence alone, cytomegalovirus (CMV) infection is thought to have major impacts on T-cell subset composition and exhaustion. These impacts have been studied extensively in TCRαβ+ T-cells, with reduction in naive, increase in effector (memory) subsets and shifts in CD4/CD8-ratios, in conjunction with morbidity and mortality in elderly. Effects of both ageing and CMV on the TCRγδ+ T-cell compartment remain largely elusive. In the current study we investigated Vγ- and Vδ-usage, maturation, differentiation and exhaustion marker profiles of both CD4 and CD8 double-negative (DN) and CD8+TCRγδ+ T-cells in 157 individuals, age range 20–95. We observed a progressive decrease in absolute numbers of total TCRγδ+ T-cells in blood, affecting the predominant Vγ9/Vδ2 population. Aged TCRγδ+ T-cells appeared to shift from naive to more (late-stage) effector phenotypes, which appeared more prominent in case of persistent CMV infections. In addition, we found effects of both ageing and CMV on the absolute counts of exhausted TCRγδ+ T-cells. Collectively, our data show a clear impact of ageing and CMV persistence on DN and CD8+TCRγδ+ T-cells, similar to what has been reported in CD8+TCRαβ+ T-cells, indicating that they undergo similar ageing processes

Differential effects of Cytomegalovirus carriage on the immune phenotype of middle-aged males and females

The elderly population is more susceptible to infections as a result of an altered immune response, commonly referred to as immunosenescence. Cytomegalovirus (CMV)-infection associated changes in blood lymphocytes are known to impact this process, but the interaction with gender remains unclear. Therefore, we analysed the effects and interaction of gender and CMV on the absolute numbers of a comprehensive set of naive and memory T- and B-cell subsets in people between 50 and 65 years of age. Enumeration and characterisation of lymphocyte subsets by flow cytometry was performed on fresh whole blood samples from 255 middle-aged persons. CMV-IgG serostatus was determined by ELISA. Gender was a major factor affecting immune cell numbers. CMV infection was mainly associated with an expansion of late-differentiated T-cell subsets. CMV+ males carried lower numbers of total CD4+, CD4+ central memory (CM) and follicular helper T-cells than females and CMV- males. Moreover, CMV+ males had significantly lower numbers of regulatory T (Treg)-cells and memory B-cells than CMV+ females. We here demonstrate an interaction between the effects of CMV infection and gender on T- and B-cells in middle-aged individuals. These differential effects on adaptive immunity between males and females may have implications for vaccination strategies at middle-age

The presence of CLL-associated stereotypic B cell receptors in the normal BCR repertoire from healthy individuals increases with age

__Background:__ Aging is known to induce immunosenescence, resulting in alterations in both the innate and adaptive immune system. Here we evaluated the effects of aging on B cell subsets in peripheral blood of 155 immunologically healthy individuals in four age categories (range 20-95y) via multi-parameter flow cytometry. Furthermore, we studied the naive and antigen-experienced B cell receptor (BCR) repertoire of different age groups and compared it to the clonal BCR repertoire of chronic lymphocytic leukemia (CLL), a disease typically presenting in elderly individuals. __Results:__ Total num

Mycophenolic acid-mediated suppression of human CD4+ T cells: more than mere guanine nucleotide deprivation

Item does not contain fulltextMycophenolic acid is the active ingredient of the immunosuppressant mycophenolate mofetil that is widely used in transplantation medicine and autoimmunity. Mycophenolic acid inhibits inosine monophosphate dehydrogenase, an enzyme involved in biosynthesis of guanine nucleotides required for lymphocyte clonal expansion. Here, we present novel insights into the mechanisms underlying mycophenolic acid-mediated suppression of human CD4+ T cells. Upon CD3/CD28 stimulation, mycophenolic acid inhibited T cell IL-17, IFN-gamma and TNF-alpha production but not IL-2 production. Phenotypic analysis showed that drug treatment enhanced the expression of negative co-stimulators PD-1, CTLA-4 and the transcription factor FoxP3 and decreased the expression of positive co-stimulators CD27 and CD28, whereas CD25 was unaffected. Mycophenolic acid-treated cells were anergic, but not suppressive, and at the same time proved hyperblastoid with high metabolic activity. Moreover, a reduced Akt/mTOR and STAT5 signaling was observed. Interestingly, the co-stimulatory molecule CD70 was uniquely and dose-dependently upregulated on mycophenolic acid-treated T cells and found to be directly linked to target enzyme inhibition. CD70 on mycophenolic acid-treated cells proved functional: an anti-CD70 agonist was found to restore both STAT5 and Akt/mTOR signaling and may thereby prevent apoptosis and promote survival. These novel insights may contribute to optimization of protocols for MPA-based immunosuppressive regimens

Iterative Filtered Backprojection Methods for Helical Cone-Beam CT

State-of-the-art reconstruction algorithms for medical helical cone-beam Computed Tomography (CT) are of type non-exact Filtered Backprojection (FBP). They are attractive because of their simplicity and low computational cost, but they produce sub-optimal images with respect to artifacts, resolution, and noise. This thesis deals with possibilities to improve the image quality by means of iterative techniques. The first algorithm, Regularized Iterative Weighted Filtered Backprojection (RIWFBP), is an iterative algorithm employing the non-exact Weighted FilteredBackprojection (WFBP) algorithm [Stierstorfer et al., Phys. Med. Biol. 49, 2209-2218, 2004] in the update step. We have measured and compared artifact reduction as well as resolution and noise properties for RIWFBP and WFBP. The results show that artifacts originating in the non-exactness of the WFBP algorithm are suppressed within five iterations without notable degradation in terms of resolution versus noise. Our experiments also indicate that the number of required iterations can be reduced by employing a technique known as ordered subsets. A small modification of RIWFBP leads to a new algorithm, the Weighted Least Squares Iterative Filtered Backprojection (WLS-IFBP). This algorithm has a slightly lower rate of convergence than RIWFBP, but in return it has the attractive property of converging to a solution of a certain least squares minimization problem. Hereby, theory and algorithms from optimization theory become applicable. Besides linear regularization, we have examined edge-preserving non-linear regularization.In this case, resolution becomes contrast dependent, a fact that can be utilized for improving high contrast resolution without degrading the signal-to-noise ratio in low contrast regions. Resolution measurements at different contrast levels and anthropomorphic phantom studies confirm this property. Furthermore, an even morepronounced suppression of artifacts is observed. Iterative reconstruction opens for more realistic modeling of the input data acquisition process than what is possible with FBP. We have examined the possibility to improve the forward projection model by (i) multiple ray models, and (ii) calculating strip integrals instead of line integrals. In both cases, for linearregularization, the experiments indicate a trade off: the resolution is improved atthe price of increased noise levels. With non-linear regularization on the other hand, the degraded signal-to-noise ratio in low contrast regions can be avoided. Huge input data sizes make experiments on real medical CT data very demanding. To alleviate this problem, we have implemented the most time consuming parts of the algorithms on a Graphics Processing Unit (GPU). These implementations are described in some detail, and some specific problems regarding parallelism and memory access are discussed

Increased expression of interleukin-22 by synovial Th17 cells during late stages of murine experimental arthritis is controlled by interleukin-1 and enhances bone degradation

Item does not contain fulltextOBJECTIVE: Interleukin-22 (IL-22) is a mediator in antimicrobial responses and inflammatory autoimmune diseases. Although IL-22 and its receptor, IL-22R, have been identified in the synovium of rheumatoid arthritis patients, the source of IL-22 and its contribution to disease pathogenicity remain to be established. This study was undertaken to investigate the regulation of IL-22 by Th17 cells in vitro and to evaluate the potential for IL-22 depletion in an experimental arthritis model using mice deficient in the IL-1 receptor antagonist (IL-1Ra-/-). METHODS: Naive murine T cells were cultured under conditions leading to polarization of the cells into subsets of Th1, Th2, induced Treg, and Th17. Cytokines were measured in the culture supernatants, and the cells were analyzed by fluorescence-activated cell sorting. Tissue samples from the inflamed ankle synovium of IL-1Ra-/- mice were isolated, and messenger RNA levels of marker genes were quantified. IL-1Ra-/- mice were treated with neutralizing anti-IL-22 antibodies. Synovial cells were isolated from the inflamed tissue and sorted into fractions for analysis of cytokine production. RESULTS: In vitro tests showed that Th17 cells produced high levels of IL-22 after stimulation with IL-1 or IL-23. Interestingly, a synergistic increase in the production of IL-22 was observed after combining IL-1 and IL-23. In vivo, IL-1Ra-/- mice displayed a progressive erosive arthritis, characterized by up-regulation of IL-17 in mildly and severely inflamed tissue, whereas the levels of IL-22 and IL-22R were increased only in severely inflamed synovia. Anti-IL-22 treatment of IL-1Ra-/- mice significantly reduced the inflammation and bone erosion. Analysis of isolated single cells from the inflamed synovia revealed that IL-22 was mainly produced by IL-17-expressing T cells. CONCLUSION: These findings suggest that IL-22 plays an important role in IL-1-driven chronic joint destruction

Selection of Self-reactive peptides within human aggrecan by use of HLA-DRB1*0401 peptide binding motif

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Targeting PKC in human T cells using sotrastaurin (AEB071) preserves regulatory T cells and prevents IL-17 production

Item does not contain fulltextRegulatory T-cells (Treg) are crucial for immune homeostasis and prevention of immune pathology. Yet, Treg may lose Foxp3 and start secreting IL-17, dependent on environmental cues. Our previous data revealed that Treg from severe psoriasis patients are particularly prone to such conversion. The question of how to maintain Treg stability in the context of inflammation awaits immediate resolution. The pan-protein kinase C (PKC) inhibitor sotrastaurin has shown efficacy in clinical trials of psoriasis. Here, we show that sotrastaurin inhibited effector T-cell responses, whereas the regulatory response was enhanced. Sotrastaurin prevented TCR/CD28-induced T-cell activation and pro-inflammatory cytokine production, but preserved a stable Treg phenotype as evidenced by maintenance of suppressive capacity, high Foxp3 and CD25 expression, and lack of IL-17A and IFNgamma production. Moreover, in both circulating and dermal psoriatic Treg, prone to rapid induction of IL-17, sotrastaurin enhanced Foxp3 expression and prevented IL-17A and IFNgamma production even when stimulated in the presence of the helper T 17-enhancing cytokines IL-1beta or IL-23. Thus, pharmacological inhibition of PKC may serve as a powerful tool to concurrently inhibit effector T cells and to facilitate Treg, thereby showing therapeutic potential for the treatment of psoriasis

CD97 antibody depletes granulocytes in mice under conditions of acute inflammation via a Fc receptor-dependent mechanism.

Item does not contain fulltextAntibodies to the pan-leukocyte adhesion-GPCR CD97 efficiently block neutrophil recruitment in mice, thereby reducing antibacterial host defense, inflammatory disease, and hematopoietic stem cell mobilization. Here, we investigated the working mechanism of the CD97 antibody 1B2. Applying sterile models of inflammation, intravital microscopy, and mice deficient for the CD97L CD55, the complement component C3, or the FcR common gamma-chain, we show that 1B2 acts in vivo independent of ligand-binding interference by depleting PMN granulocytes in bone marrow and blood. Granulocyte depletion with 1B2 involved FcR but not complement activation and was associated with increased serum levels of TNF and other proinflammatory cytokines. Notably, depletion of granulocytes by CD97 antibody required acute inflammation, suggesting a mechanism of conditional, antibody-mediated granulocytopenia.1 maart 201