Regulatory immune cells in transplantation

Immune regulation is fundamental to any immune response to ensure that it is appropriate for the perceived threat to the host. Following cell and organ transplantation, it is essential to control the innate immune response triggered by the injured tissue and the adaptive immune response stimulated by mismatched donor and recipient histocompatibility antigens if the transplant is going to survive and function. Here, we discuss the leukocyte populations that can promote tolerogenic immune responses after cell or solid-organ transplantation. Such populations include regulatory T cells, B cells and macrophages, as well as myeloid-derived suppressor cells, dendritic cells and mesenchymal stromal cells. We consider the potential of these regulatory immune cells to develop and function in transplant recipients and their potential use as cellular therapies to promote long term graft function

High-Q photonic crystal cavities in all-semiconductor photonic-crystal heterostructures

Photonic crystal cavities enable the realization of high Q-factor and low mode-volume resonators, with typical architectures consisting of a thin suspended periodically-patterned layer to maximize confinement of light by strong index guiding. We investigate a heterostructure-based approach comprising a high refractive index core and lower refractive index cladding layers. Whilst confinement typically decreases with decreasing index contrast between the core and cladding layers, we show that, counter-intuitively, due to the confinement provided by the photonic band structure in the cladding layers, it becomes possible to achieve Q-factors $>10^4$ with only a small refractive index contrast. This opens up new opportunities for implementing high Q-factor cavities in conventional semiconductor heterostructures, with direct applications to the design of electrically-pumped nano-cavity lasers using conventional fabrication approaches

Advances in imaging of new targets for pharmacological intervention in stroke: real-time tracking of T-cells in the ischaemic brain

Background and purpose: T‐cells may play a role in the evolution of ischaemic damage and repair, but the ability to image these cells in the living brain after a stroke has been limited. We aim to extend the technique of real‐time in situ brain imaging of T‐cells, previously shown in models of immunological diseases, to models of experimental stroke. Experimental approach: Male C57BL6 mice (6–8 weeks) (n= 3) received a total of 2–5 × 106 carboxyfluorescein diacetate succinimidyl ester (CFSE)‐labelled lymphocytes from donor C57BL6 mice via i.v. injection by adoptive transfer. Twenty‐four hours later, recipient mice underwent permanent left distal middle cerebral artery occlusion (MCAO) by electrocoagulation or by sham surgery under isoflurane anaesthesia. Female hCD2‐green fluorescent protein (GFP) transgenic mice that exhibit GFP‐labelled T‐cells underwent MCAO. At 24 or 48 h post‐MCAO, a sagittal brain slice (1500 µm thick) containing cortical branches of the occluded middle cerebral artery (MCA) was dissected and used for multiphoton laser scanning microscopy (MPLSM). Key results: Our results provide direct observations for the first time of dynamic T‐cell behaviour in living brain tissue in real time and herein proved the feasibility of MPLSM for ex vivo live imaging of immune response after experimental stroke. Conclusions and Implications: It is hoped that these advances in the imaging of immune cells will provide information that can be harnessed to a therapeutic advantage

MiR-142-3p is downregulated in aggressive p53 mutant mouse models of pancreatic ductal adenocarcinoma by hypermethylation of its locus

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease with poor prognostic implications. This is partly due to a large proportion of PDACs carrying mutations in TP53, which impart gain-of-function characteristics that promote metastasis. There is evidence that microRNAs (miRNAs) may play a role in both gain-of-function TP53 mutations and metastasis, but this has not been fully explored in PDAC. Here we set out to identify miRNAs which are specifically dysregulated in metastatic PDAC. To achieve this, we utilised established mouse models of PDAC to profile miRNA expression in primary tumours expressing the metastasis-inducing mutant p53R172H and compared these to two control models carrying mutations, which promote tumour progression but do not induce metastasis. We show that a subset of miRNAs are dysregulated in mouse PDAC tumour tissues expressing mutant p53R172H, primary cell lines derived from mice with the same mutations and in TP53 null cells with ectopic expression of the orthologous human mutation, p53R175H. Specifically, miR-142-3p is downregulated in all of these experimental models. We found that DNA methyltransferase 1 (Dnmt1) is upregulated in tumour tissue and cell lines, which express p53R172H. Inhibition or depletion of Dnmt1 restores miR-142-3p expression. Overexpression of miR-142-3p attenuates the invasive capacity of p53R172H-expressing tumour cells. MiR-142-3p dysregulation is known to be associated with cancer progression, metastasis and the miRNA is downregulated in patients with PDAC. Here we link TP53 gain-of-function mutations to Dnmt1 expression and in turn miR-142-3p expression. Additionally, we show a correlation between expression of these genes and patient survival, suggesting that they may have potential to be therapeutic targets

Looking out for Lottie an inter-professional training pack

A 37 page inter-professional training pack with a literature review and worksheet

‘Our voice started off as a whisper and now it is a great big roar’ : The Salford Dementia Associate Panel as a model of involvement in research activities

This paper presents the work of the ‘Salford Dementia Associate Panel’, based at the Salford Institute for Dementia, Salford University (UK). We discuss the roles of the Dementia Associates, in particular around the areas of engagement and research. The panel is made up of people living with dementia, and current and former care partners. It highlights the development of this group over a four-year period and demonstrates over time how the role of a Dementia Associate member has evolved. The panel is involved in research, education and public engagement activities conducted by staff and students within the Institute. The motivations for becoming involved are clearly articulated and demonstrate how the personal backgrounds of individuals have driven the collective involvement and desire to bring about change. The benefits and challenges associated with working as part of a panel are discussed. We conclude by bringing together our experiences as a set of suggestions for others who may wish to create a similar forum to promote the involvement of people living with dementia and former and current care partners

A 340/380 nm light emitting diode illuminator for Fura-2 AM ratiometric Ca2+ imaging of live cells with better than 5 nM precision

Cytosolic Ca2+ plays an integral role in cells and the study of its dynamics can reveal much about biological processes [1]. Fura-2 can provide quantitative data on cytosolic Ca2+ changes by exciting at 340 nm and 380 nm and taking the ratio of the emission at both wavelengths [2]. Traditionally for this type of imaging an arc lamp had to be used for illumination as LEDs of the appropriate wavelengths were not available [3]. LEDs hold advantages over arc lamps by exhibiting high amplitude stability and the ability to rapidly switch between wavelengths. We aimed to test a new 340/380 nm LED system for use in ratiometric Fura-2 AM Ca2+ imaging and present results using tsA-201 cells and hippocampal neurons

Nonconvolution nonlinear integral Volterra equations with monotone operators

Some results about existence, uniqueness, and attractive behaviour of solutions for nonlinear Volterra integral equations with non-convolution kernels are presented in this paper. These results are based on similar ones about nonlinear Volterra integral equations with convolution kernels and some comparison techniques. Therefore, this paper is devoted to find a wide class of nonconvolution Volterra integral equations where their solutions behave like those of Volterra equations with convolution kernels.Comment: 13 page