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"Richards, James"
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A comparison of currently available optoelectronic motion capture systems
The measurement of human motion relies heavily on the ability of the optoelectronic motion capture systems to accurately measure retroreflective marker positions. Marker position accuracy is largely dependent on the optical characteristics of the camera system and algorithms implemented in the tracking software. In 1999, Richards critically reviewed multiple camera systems and each of their ability to generate the same marker coordinate positions under different field tests. Field tests were designed utilizing what became to be known as the Standard Assessment of Motion System Accuracy (SAMSA) device. The SAMSA test results indicated that some systems outperformed others and accuracy varied depending on the test. In the subsequent 20 years, motion capture technology has significantly improved. Therefore, we aimed to replicate the tests from 1999 using current, higher-resolution motion capture systems and current calibration techniques. Reference marker distances were established utilizing a FaroArm 3D digitizer (FARO technologies). The modern cameras field test performance showed nearly a three-fold improvement in agreement with the reference measure compared to their 1999 predecessors. No systems’ absolute marker distance measured greater than 0.5 mm from the FaroArm measurement and no systems’ maximum error exceeded 1.0 mm. Given the consistency in accuracy reported by all the systems included in the current assessment, it’s reasonable to assume that the current systems would eliminate errors associated with system hardware/software as an obstacle to sharing data between laboratories.
Journal Article
T cell Allorecognition Pathways in Solid Organ Transplantation
Transplantation is unusual in that T cells can recognize alloantigen by at least two distinct pathways: as intact MHC alloantigen on the surface of donor cells via the direct pathway; and as self-restricted processed alloantigen via the indirect pathway. Direct pathway responses are viewed as strong but short-lived and hence responsible for acute rejection, whereas indirect pathway responses are typically thought to be much longer lasting and mediate the progression of chronic rejection. However, this is based on surprisingly scant experimental evidence, and the recent demonstration that MHC alloantigen can be re-presented intact on recipient dendritic cells-the semi-direct pathway-suggests that the conventional view may be an oversimplification. We review recent advances in our understanding of how the different T cell allorecognition pathways are triggered, consider how this generates effector alloantibody and cytotoxic CD8 T cell alloresponses and assess how these responses contribute to early and late allograft rejection. We further discuss how this knowledge may inform development of cellular and pharmacological therapies that aim to improve transplant outcomes, with focus on the use of induced regulatory T cells with indirect allospecificity and on the development of immunometabolic strategies.
Acute allograft rejection is likely mediated by indirect and direct pathway CD4 T cell alloresponses.Chronic allograft rejection is largely mediated by indirect pathway CD4 T cell responses. Direct pathway recognition of cross-dressed endothelial derived MHC class II alloantigen may also contribute to chronic rejection, but the extent of this contribution is unknown.Late indirect pathway CD4 T cell responses will be composed of heterogeneous populations of allopeptide specific T helper cell subsets that recognize different alloantigens and are at various stages of effector and memory differentiation.Knowledge of the precise indirect pathway CD4 T cell responses active at late time points in a particular individual will likely inform the development of alloantigen-specific cellular therapies and will guide immunometabolic modulation.
Journal Article
Interactions between interfaces dictate stimuli-responsive emulsion behaviour
Stimuli-responsive emulsions offer a dual advantage, combining long-term storage with controlled release triggered by external cues such as pH or temperature changes. This study establishes that thermo-responsive emulsion behaviour is primarily determined by interactions between, rather than within, interfaces. Consequently, the stability of these emulsions is intricately tied to the nature of the stabilizing microgel particles - whether they are more polymeric or colloidal, and the morphology they assume at the liquid interface. The colloidal properties of the microgels provide the foundation for the long-term stability of Pickering emulsions. However, limited deformability can lead to non-responsive emulsions. Conversely, the polymeric properties of the microgels enable them to spread and flatten at the liquid interface, enabling stimuli-responsive behaviour. Furthermore, microgels shared between two emulsion droplets in flocculated emulsions facilitate stimuli-responsiveness, regardless of their internal architecture. This underscores the pivotal role of microgel morphology and the forces they exert on liquid interfaces in the control and design of stimuli-responsive emulsions and interfaces.
Stimuli-responsive emulsions are useful for long-term storage combined with controlled release, but the fundamental mechanism behind this release is not established. Here, the authors report a study into the effect of individual microgel morphology on the destabilisation of responsive emulsions.
Journal Article
Life
An autobiography of the singer, songwriter, guitarist and founding member of the Rolling Stones.
Book
Decreased maternal serum acetate and impaired fetal thymic and regulatory T cell development in preeclampsia
Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preeclampsia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preeclamptic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4
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T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preeclampsia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preeclampsia and immune development in offspring.
Maternal immunological dysregulation might affect the immunological development of the fetus. Here the authors show that decreased maternal acetate is associated with preeclampsia, impaired fetal thymic output and regulatory T cell development.
Journal Article
Gut microbial metabolites limit the frequency of autoimmune T cells and protect against type 1 diabetes
The gut microbiota can influence immune-cell function by the production of short-chain fatty acids. Mackay and colleagues show that diets enriched for acetate and butyrate protect non-obese diabetic mice from insulitis and diabetes progression.
Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon. Each diet provided a high degree of protection from diabetes, even when administered after breakdown of immunotolerance. Feeding mice a combined acetate- and butyrate-yielding diet provided complete protection, which suggested that acetate and butyrate might operate through distinct mechanisms. Acetate markedly decreased the frequency of autoreactive T cells in lymphoid tissues, through effects on B cells and their ability to expand populations of autoreactive T cells. A diet containing butyrate boosted the number and function of regulatory T cells, whereas acetate- and butyrate-yielding diets enhanced gut integrity and decreased serum concentration of diabetogenic cytokines such as IL-21. Medicinal foods or metabolites might represent an effective and natural approach for countering the numerous immunological defects that contribute to T cell–dependent autoimmune diseases.
Journal Article