The effect of macrophage polarisation on adipose tissue fibrosis in the context of hyperinsulinaemia

In obesity, adipose tissue (AT) must remodel to accommodate adipocyte expansion. This remodelling is achieved through degradation and synthesis of extracellular matrix (ECM) components. Obese AT fibrosis, where excess fibrous ECM proteins accumulate, is thought to limit lipid storage capacity, leading to AT dysfunction and pathogenic ectopic lipid deposition. Dysfunctional AT is strongly associated with insulin resistance and characterised by low-level inflammation and increased macrophage infiltration. AT macrophages are classified as pro-inflammatory M1, or anti-inflammatory M2 (including M2a and M2c subtypes). M2 macrophage-secreted factors, as well as high levels of insulin, may induce AT fibrosis development thus increasing AT dysfunction. This study aimed to understand the role of polarised macrophage phenotypes and hyperinsulinaemia on the development of AT fibrosis. THP-1 monocytes were differentiated and resulting macrophage phenotypes analysed by protein secretion and macrophage marker mRNA quantification. Macrophages were co-cultured with human omental AT explants (age: 49.5±7.83, BMI: 27.98±6.12) with vehicle-only, 1nM, 10nM or 100nM insulin for 48h before AT expression of fibrosis-associated genes was measured using qRT-PCR. Macrophage characterisation suggested M (IFNγ+LPS) macrophages possessed a mixed M1/M2 phenotype, M (IL-4) macrophages were broadly M2-like, while M (IL-10) macrophages were considered not functionally differentiated. Co-culture with M (IFNγ+LPS) macrophages significantly upregulated FN1 (3.6±3.07 mean fold increase ±SD), and M (IL-4) macrophages upregulated molecular mediators of fibrosis LOX and SPARC (1.98±1.2 and 1.61±0.74) in AT. Under hyperinsulinaemic conditions (1nM or 10nM insulin) with M (IFNγ+LPS) macrophages, AT COL4A1, COL5A3, TGFB1 and FN1 were downregulated (0.78±0.13, 0.956±0.53, 1.00±0.34, 2.32±1.3 respectively) compared to the vehicle control. Results suggest that mixed M1/M2 phenotype and M2-like macrophages may contribute to AT fibrosis, and hyperinsulinaemic conditions may moderate this effect. However, poor experimental design and inadequate optimisation prevented scientifically sound conclusions being drawn from this study. Further comprehensive work is required to determine the role of macrophages and hyperinsulinaemia in AT fibrosis

Radioresistance of Brain Tumors

Radiation therapy (RT) is frequently used as part of the standard of care treatment of the majority of brain tumors. The efficacy of RT is limited by radioresistance and by normal tissue radiation tolerance. This is highlighted in pediatric brain tumors where the use of radiation is limited by the excessive toxicity to the developing brain. For these reasons, radiosensitization of tumor cells would be beneficial. In this review, we focus on radioresistance mechanisms intrinsic to tumor cells. We also evaluate existing approaches to induce radiosensitization and explore future avenues of investigation

Learning from where ‘eye’ remotely look or point: impact on number line estimation error in adults.

In this paper we present an investigation into the use of visual cues during number line estimation, and their influence on cognitive processes for reducing number line estimation error. Participants completed a 0-1000 number line estimation task pre and post a brief intervention in which they observed static-visual or dynamicvisual cues (control, anchor, gaze cursor, mouse cursor) and also made estimation marks to test effective number-target estimation. Results indicated that a significant pre-test to post-test reduction in estimation error was present for dynamic visual cues of modelled eye-gaze and mouse-cursor. However, there was no significant performance difference between pre and post-test for the control or static anchor conditions. Findings are discussed in relation to the extent to which anchor points alone are meaningful in promoting successful segmentation of the number line, and whether dynamic cues promote the utility of these locations in reducing error through attentional guidance

Examining the response programming function of the Quiet Eye: Do tougher shots need a quieter eye?

This is the author accepted manuscript. The final version is available from Springer Verlag via the DOI in this record.Support for the proposition that the Quiet Eye (QE) duration reflects a period of response programming (including task parameterisation) has come from research showing that an increase in task difficulty is associated with increases in QE duration. Here, we build on previous research by manipulating three elements of task difficulty that correspond with different parameters of golf-putting performance; force production, impact quality and target line. Longer QE durations were found for more complex iterations of the task and furthermore, more sensitive analyses of the QE duration suggest that the early QE proportion (prior to movement initiation) is closely related to force production and impact quality. However, these increases in QE do not seem functional in terms of supporting improved performance. Further research is needed to explore QE's relationship with performance under conditions of increased difficulty

A new grapevine yellows phytoplasma from the Buckland Valley of Victoria, Australia

A new phytoplasma detected in grapevines with grapevine yellows disease from the Buckland Valley of Victoria, Australia was characterized. Buckland Valley grapevine yellows phytoplasma (BVGYp) could not be amplified by PCR using primers specific for the stolbur (STOL, 16SrXII) group of phytoplasmas indicating that it was unlikely to be a STOL group phytoplasma. BVGYp was amplified by PCR using primers specific for both the aster yellows (AV, 16Sr I) and STOL phytoplasma groups, indicating that it may be more closely related to the AY group phytoplasmas. Sequence analysis of 16SrRNA gene sequences showed that BVGYp clustered with AY and STOL groups of phytoplasmas. Sequence similarities were determined by pairwise comparisons of the 16S rDNA sequence of BVGYp WAY and STOL group phytoplasmas and BVGYp was more closely related to the AY group phytoplasmas. Although the data indicate BVGYp may form a newAY subgroup, the similarity coefficients between BVGYp and phytoplasmas from the AY, STOL and Mexican periwinkle virescence groups, derived from putative RFLP patterns, were less than 90%, so BVGYp may actually form a new phytoplasma group.

The genetic control of avascular area in mouse oxygen-induced retinopathy

Purpose: The C57BL/6ByJ and BALB/cByJ inbred strains of mice are, respectively, susceptible and resistant to oxygen-induced retinopathy (OIR). The purpose of this work was to investigate the genetic control of the retinal avascular area in mouse OIR using a mapping cross. Methods: The central retinal avascular area was measured on postnatal day 16 (P16) in C57BL/6ByJ, BALB/cByJ, 101 (C57BL/6ByJ x BALB/cByJ)F2, and 116 (BALB/cByJ x C57BL/6ByJ)F2 mice that had been subjected to the OIR protocol. A genome-wide scan was performed of selected albino and non-albino mice to determine quantitative trait loci associated with weight and avascular area. Results: C57BL/6ByJ mice had significantly larger avascular areas than BALB/cByJ ones. Albino mice of the F2 generation had smaller avascular areas than the non-albino mice. Genotyping was performed at 856 informative single nucleotide polymorphisms approximately evenly distributed across the genome from each of 85 selected F2 mice. Weight, sex, and the paternal grandmother were found to act as additive covariates associated with the avascular area on P16; mapping analyses that used a model incorporating these covariates found a quantitative trait locus on chromosome 7 related to avascular area. Mapping analyses that used a model that did not incorporate covariates found a quantitative trait locus on chromosome 9 related to avascular area. A quantitative trait locus for bodyweight on P16 was mapped to chromosome 5. Conclusions: The retinal avascular area in the mouse OIR model is under genetic control. Revascularization in OIR is related to the weight, strain of paternal grandmother, sex, and albinism. Our data support the existence of a quantitative trait locus on chromosome 5 that influences weight after exposure to hyperoxia, as well as quantitative trait loci on chromosomes 7 and 9 that modify susceptibility to OIR