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Low Bone Turnover in Chronic Kidney Disease is associated with decreased VEGF-A expression and osteoblast differentiation

Background: Low turnover bone (low bone formation rates (BFRs)) with decreased osteoblast number is common in patients with chronic kidney disease (CKD) and attributed to ‘over-suppression' of the parathyroid hormone (PTH) despite supra-physiologic levels. An alternative hypothesis is abnormal osteoblast differentiation, resulting in low BFRs due to reduced VEGF-A. Methods: We analyzed the expression of VEGF-A and mesenchymal stem cell (MSC) differentiation factors in freshly isolated bone marrow (BM) cells, and in BM cell-derived MSC in rats with different levels of BFRs and PTH (modulated by calcium and zoledronic acid). The regulators of VEGF in MSC were also determined. Results: VEGF-A expression was reduced in the BM cells from CKD vs. normal animals (p < 0.02). In BM-derived MSC from CKD, there were decreased osteoblast transcription factors and mineralization. In CKD animals, the BM VEGF-A expression was positively correlated with BFR (r = 0.80, p < 0.001). Reducing BFRs in CKD animals led to reductions in VEGF-A expression and osteoblast transcription factors regardless of the PTH level. We therefore examined other regulators of VEGF-A and found decreased expression of hypoxia-inducible factor-1α and the master transcription factor of antioxidants nuclear factor (erythroid-derived 2)-like 2 in CKD animals with low PTH. Conclusion: Low BFRs in CKD are associated with a basal decrease in VEGF-A expression in BM that may be driven by altered hypoxia and oxidative stress

Transcription-Independent Heritability of Induced Histone Modifications in the Mouse Preimplantation Embryo

Enzyme-catalyzed, post-translational modifications of core histones have been implicated in the complex changes in gene expression that drive early mammalian development. However, until recently the small number of cells available from the preimplantation embryo itself has prevented quantitative analysis of histone modifications at key regulator genes. The possible involvement of histone modifications in the embryo's response to extracellular signals, or as determinants of cell fate or lineage progression, remains unclear. Here we describe the use of a recently-developed chromatin immunoprecipitation technique (CChIP) to assay histone modification levels at key regulator genes (Pou5f1, Nanog, Cdx2, Hoxb1, Hoxb9) as mouse embryos progress from 8-cell to blastocyst in culture. Only by the blastocyst stage, when the embryonic (Inner Cell Mass) and extra-embryonic (Trophoblast) lineages are compared, do we see the expected association between histone modifications previously linked to active and silent chromatin, and transcriptional state. To explore responses to an environmental signal, we exposed embryos to the histone deacetylase inhibitor, anti-epileptic and known teratogen valproic acid (VPA), during progression from 8-cell to morula stage. Such treatment increased H4 acetylation and H3 lysine 4 methylation at the promoters of Hoxb1 and Hoxb9, but not the promoters of Pou5f1, Nanog,Cdx2 or the housekeeping gene Gapdh. Despite the absence of detectable Hoxb transcription, these VPA-induced changes were heritable, following removal of the inhibitor, at least until the blastocyst stage. The selective hyperacetylation of Hoxb promoters in response to a histone deacetylase inhibitor, suggests that Hox genes have a higher turnover of histone acetates than other genes in the preimplantation embryo. To explain the heritability, through mitosis, of VPA-induced changes in histone modification at Hoxb promoters, we describe how an epigenetic feed-forward loop, based on cross-talk between H3 acetylation and H3K4 methylation, might generate a persistently increased steady-state level of histone acetylation in response to a transient signal

A Fortuitous Syncope. The pitfalls of Integrated Bipolar Defibrillator Leads

Myopotential oversensing in implantable defibrillators causing inhibition of pacing and inappropriate therapies is well described. Current literature is dominated by reports of diaphragmatic muscle as the source of such far-field oversensing. Those reporting pectoral muscle sources were invariably due to unipolar sensing circuits, incorrect DF-1 connections or inappropriate programming. We report an interesting case of pectoral muscle myopotential oversensing causing inhibition of bradycardia pacing leading to presyncope and syncope

Feasibility of [F-18]fluoropivalate hybrid PET/MRI for imaging lower and higher grade glioma: a prospective first-in-patient pilot study

Purpose: MRI and PET are used in neuro-oncology for the detection and characterisation of lesions for malignancy to target surgical biopsy and to plan surgical resections or stereotactic radiosurgery. The critical role of short-chain fatty acids (SCFAs) in brain tumour biology has come to the forefront. The non-metabolised SCFA radiotracer, [18F]fluoropivalate (FPIA), shows low background signal in most tissues except eliminating organs and has appropriate human dosimetry. Tumour uptake of the radiotracer is, however, unknown. We investigated the uptake characteristics of FPIA in this pilot PET/MRI study. Methods: Ten adult glioma subjects were identified based on radiological features using standard-of-care MRI prior to any surgical intervention, with subsequent histopathological confirmation of glioma subtype and grade (lower-grade – LGG – and higher-grade – HGG – patients). FPIA was injected as an intravenous bolus injection (range 342–368 MBq), and dynamic PET and MRI data were acquired simultaneously over 66 min. Results: All patients tolerated the PET/MRI protocol. Three patients were reclassified following resection and histology. Tumour maximum standardised uptake value (SUVmax,60) increased in the order LGG (WHO grade 2) < HGG (WHO grade 3) < HGG (WHO grade 4). The net irreversible solute transfer, Ki, and influx rate constant, K1, were significantly higher in HGG (p < 0.05). Of the MRI variables studied, DCE-MRI-derived extravascular-and-extracellular volume fraction (ve) was high in tumours of WHO grade 4 compared with other grades (p < 0.05). SLC25A20 protein expression was higher in HGG compared with LGG. Conclusion: Tumoural FPIA PET uptake is higher in HGG compared to LGG. This study supports further investigation of FPIA PET/MRI for brain tumour imaging in a larger patient population. Clinical trial registration: Clinicaltrials.gov, NCT04097535

Stock assessment of Australian east coast snapper, Chrysophrys auratus Predictions of stock status and reference points for 2016

Snapper, Chrysophrys auratus, is a valuable commercial, recreational and charter fish species throughout its temperate/subtropical range along Australia’s east coast. East coast snapper form a single genetic stock in ocean waters between Mackay (21.50S) in northern Queensland and about Eden (380S) in southern New South Wales. Fish in this eastern coast stock have been recorded to live for up to 41 years, with maturity occurring at four years of age. This is the first assessment for the whole east coast stock. This comprehensive snapper stock assessment includes commercial, recreational and charter data sets from both New South Wales and Queensland (up to 2016). The assessment grouped the dynamics of the fishery into four fishing sectors: namely, 1) New South Wales commercial trap fishing, 2) New South Wales commercial and charter line, 3) Queensland commercial and charter line and 4) New South Wales and Queensland recreational. Changes in management arrangements through time were incorporated

An MRS- and PET-guided biopsy tool for intraoperative neuronavigational systems

OBJECTIVEGlioma heterogeneity and the limitations of conventional structural MRI for identifying aggressive tumor components can limit the reliability of stereotactic biopsy and, hence, tumor characterization, which is a hurdle for developing and selecting effective treatment strategies. In vivo MR spectroscopy (MRS) and PET enable noninvasive imaging of cellular metabolism relevant to proliferation and can detect regions of more highly active tumor. Here, the authors integrated presurgical PET and MRS with intraoperative neuronavigation to guide surgical biopsy and tumor sampling of brain gliomas with the aim of improving intraoperative tumor-tissue characterization and imaging biomarker validation.METHODSA novel intraoperative neuronavigation tool was developed as part of a study that aimed to sample high-choline tumor components identified by multivoxel MRS and 18F-methylcholine PET-CT. Spatially coregistered PET and MRS data were integrated into structural data sets and loaded onto an intraoperative neuronavigation system. High and low choline uptake/metabolite regions were represented as color-coded hollow spheres for targeted stereotactic biopsy and tumor sampling.RESULTSThe neurosurgeons found the 3D spherical targets readily identifiable on the interactive neuronavigation system. In one case, areas of high mitotic activity were identified on the basis of high 18F-methylcholine uptake and elevated choline ratios found with MRS in an otherwise low-grade tumor, which revealed the possible use of this technique for tumor characterization.CONCLUSIONSThese PET and MRI data can be combined and represented usefully for the surgeon in neuronavigation systems. This method enables neurosurgeons to sample tumor regions based on physiological and molecular imaging markers. The technique was applied for characterizing choline metabolism using MRS and 18F PET; however, this approach provides proof of principle for using different radionuclide tracers and other MRI methods, such as MR perfusion and diffusion.</jats:sec

Assessment of the blue swimmer crab (Portunus armatus) fishery in Queensland

The blue swimmer crab (BSC) fishery in Queensland has undergone considerable change since its development in the middle of the 20th century. In the last 30 years the fishery has progressed to being fully fished with the expansion of crab-pot fisheries to areas outside of Moreton Bay. After the implementation of the Fisheries (East Coast Trawl) Management Plan 1999, the reported harvest from the trawl sector decreased significantly, with the commercial and recreational crab-pot sectors now accounting for the majority of the reported blue swimmer crab harvest. The commercial pot fisheries outside Moreton Bay also developed rapidly in the late 1990s. Concerns have been raised by a number of crab-pot fishers about poor economic viability under current management rules and reduced catch rates from a number of Moreton and Hervey Bay areas. This research and publication was requested by fisheries management to assess reasons for declining catch rates and profits, including evidence associated with overfishing, crab reproduction and disease, and flood events. The analyses undertaken during the current study suggested that the blue swimmer crab population was not overfished to the point where the spawning biomass was significantly reduced. However, the current levels of population size of male legal crab and fishing effort were not suitable to produce acceptable levels of catch rates for economic profit or angling quality. Analysis of the reproductive characters of the blue swimmer crab from fished areas of Moreton Bay has shown no significant changes in key indicators since research was conducted in the mid 1980’s. Similarly, the levels of fertilization of immediate post-moult female crabs have remained unchanged in the past 30 years. There was no evidence of declines in fertilization rate as all females assessed had >90% of eggs successfully developing. There was evidence to suggest a decline in the size of females, despite the fact that females are not legally fished. The levels of parasitism and disease were found to be low and have not changed significantly in the last 30 years. Levels of parasitism by Sacculina granifera have declined. Environmental factors have been shown to influence blue swimmer crab fisheries in both Cockburn Sound and Shark Bay in Western Australia, but we found no conclusive evidence to support similar effects in Queensland. Declining catch rates appear to be related to overly competitive fishing, resulting in a smaller population size of male legal crab. Increases in the number of pots used by fishers in all regions is likely a result of escalating costs of fishing, particularly fuel, impacting on profits due to declining beach price relative to inflation. To cure this state, the data and analyses indicate that effort reduction is required in order to significantly improve catch rates and generate economic profits. A range of maximum economic yields were calculated for the Moreton and Hervey Bay regions, so that a meaningful upper limit on license numbers and total allowable fishing effort can be evaluated. Effort reductions of 50% to 70% may be required in order to maximise vessel based profit. The evaluation of raising the minimum legal size (MLS) in order to reduce fishing pressure indicates that this would have a negative impact on fishery economics

Bycatch weight, composition and preliminary estimates of the impact of bycatch reduction devices in Queensland's trawl fishery

This report provides quantitative information on the effects of turtle excluder devices (TEDs) and bycatch reduction devices (BRDs) on the catch rates of bycatch, prawns, scallops and byproduct species, such as Moreton Bay bugs and Balmain bugs, in Queensland’s major trawl fishing sectors. It also provides biological information on, and management advice for several species referred to in the Fishery Management Plan as the permitted species. Several recommendations are included for reducing bycatch in the trawl fishery and for sustaining stocks of the permitted species