Histological Evaluation of Corneal Scar Formation in Pseudophakic Bullous Keratopathy

PURPOSE: To evaluate histological changes in the corneal stroma in pseudophakic bullous keratopathy. METHODS: Twenty-eight patients (28 eyes) with pseudophakic bullous keratopathy underwent therapeutic penetrating keratoplasty at Shandong Eye Institute between January 2006 and November 2011. The patients were divided into two groups according to the duration of bullous keratopathy (<1.0 year group or >1.0 year group), and three buttons from enucleated eyes with choroidal melanoma served as a control. In vivo confocal microscopy examination, hematoxylin-eosin, Masson's trichrome stain and Van Gieson staining were used for microscopic examination. The histological evaluation and scoring of the buttons for morphological changes, including the degree of stromal scars, neovascularization and inflammatory cells within the corneal buttons, were compared. To study the underlying mechanism, connective tissue growth factor (CTGF) and TGF-β immunohistochemistry were performed. RESULTS: Confocal microscopy examination and histological evaluation and scoring of the buttons showed that compared with the <1.0 year group, stromal scars, neovascularization and inflammatory cells were more severe in the >1.0 year group (P<0.05). There was an increase in CTGF- and TGF-β1-positive stromal cells in the >1.0 year group. CONCLUSIONS: During the progression of pseudophakic bullous keratopathy, stromal scars occurred more often in the patients that had a longer duration of disease. Cytokines such as CTGF and TGF-β1 may play a role in this pathological process and deserve further investigation

TISs-ST: a web server to evaluate polymorphic translation initiation sites and their reflections on the secretory targets

<p>Abstract</p> <p>Background</p> <p>The nucleotide sequence flanking the translation initiation codon (start codon context) affects the translational efficiency of eukaryotic mRNAs, and may indicate the presence of an alternative translation initiation site (TIS) to produce proteins with different properties. Multi-targeting may reflect the translational variability of these other protein forms. In this paper we present a web server that performs computations to investigate the usage of alternative translation initiation sites for the synthesis of new protein variants that might have different functions.</p> <p>Results</p> <p>An efficient web-based tool entitled TISs-ST (Translation Initiation Sites and Secretory Targets) evaluates putative translation initiation sites and indicates the prediction of a signal peptide of the protein encoded from this site. The TISs-ST web server is freely available to both academic and commercial users and can be accessed at <url>http://ipe.cbmeg.unicamp.br/pub/TISs-ST</url>.</p> <p>Conclusion</p> <p>The program can be used to evaluate alternative translation initiation site consensus with user-specified sequences, based on their composition or on many position weight matrix models. TISs-ST provides analytical and visualization tools for evaluating the periodic frequency, the consensus pattern and the total information content of a sequence data set. A search option allows for the identification of signal peptides from predicted proteins using the PrediSi software.</p

Synchronization modulation increases transepithelial potentials in MDCK monolayers through Na/K pumps

Peer reviewedPublisher PD

Zealots Attack and the Revenge of the Commons: Quality vs Quantity in the Best-of-n

© 2020, Springer Nature Switzerland AG. In this paper we study the effect of inflexible individuals with fixed opinions, or zealots, on the dynamics of the best-of-n collective decision making problem, using both the voter model and the majority rule decision mechanisms. We consider two options with different qualities, where the lower quality option is associated to a higher number of zealots. The aim is to study the trade-off between option quality and zealot quantity for two different scenarios: one in which all agents can modulate dissemination of their current opinion proportionally to the option quality, and one in which this capability is only possessed by the zealots. In both scenarios, our goal is to determine in which conditions consensus is more biased towards the high or low quality option, and to determine the indifference curve separating these two regimes. Using both numerical simulations and ordinary differential equation models, we find that: i) if all agents can modulate the dissemination time based on the option quality, then consensus can be driven to the high quality option when the number of zealots for the other option is not too high; ii) if only zealots can modulate the dissemination time based on the option quality, whil e all normal agents cannot distinguish the two options and cannot differentially disseminate, then consensus no longer depends on the quality and is driven to the low quality option by the zealots

Fermentation by Lactobacillus enhances anti-inflammatory effect of Oyaksungisan on LPS-stimulated RAW 264.7 mouse macrophage cells

<p>Abstract</p> <p>Background</p> <p>Oyaksungisan (OY) has been used as a traditional drug in east-Asian countries. However, its effect on inflammation still remains unknown. In this study, to provide insight into the biological effects of OY and OY fermented by <it>Lactobacillus</it>, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in the RAW 264.7 murine macrophage cells.</p> <p>Methods</p> <p>The investigation was focused on whether OY and fermented OYs could inhibit the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin (PG) E₂as well as the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW 264.7 cells.</p> <p>Results</p> <p>We found that OY inhibits a little LPS-induced NO, PGE₂, TNF-α and IL-6 productions as well as the expressions of iNOS and COX-2. Interestingly, the fermentation significantly increased its inhibitory effect on the expression of all pro-inflammatory mediators. Furthermore, the fermented OYs exhibited elevated inhibition on the translocation of NF-κB p65 through reduced IκBα degradation as well as the phosphorylations of extracellular signal-regulated kinase (ERK), p38 and c-Jun NH₂-terminal kinase (JNK) MAPKs than untreated control or original OY.</p> <p>Conclusions</p> <p>Finally, the fermentation by <it>Lactobacillus </it>potentiates the anti-inflammatory effect of OY by inhibiting NF-κB and MAPK activity in the macrophage cells.</p

Seasonal changes in patterns of gene expression in avian song control brain regions.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Photoperiod and hormonal cues drive dramatic seasonal changes in structure and function of the avian song control system. Little is known, however, about the patterns of gene expression associated with seasonal changes. Here we address this issue by altering the hormonal and photoperiodic conditions in seasonally-breeding Gambel's white-crowned sparrows and extracting RNA from the telencephalic song control nuclei HVC and RA across multiple time points that capture different stages of growth and regression. We chose HVC and RA because while both nuclei change in volume across seasons, the cellular mechanisms underlying these changes differ. We thus hypothesized that different genes would be expressed between HVC and RA. We tested this by using the extracted RNA to perform a cDNA microarray hybridization developed by the SoNG initiative. We then validated these results using qRT-PCR. We found that 363 genes varied by more than 1.5 fold (>log(2) 0.585) in expression in HVC and/or RA. Supporting our hypothesis, only 59 of these 363 genes were found to vary in both nuclei, while 132 gene expression changes were HVC specific and 172 were RA specific. We then assigned many of these genes to functional categories relevant to the different mechanisms underlying seasonal change in HVC and RA, including neurogenesis, apoptosis, cell growth, dendrite arborization and axonal growth, angiogenesis, endocrinology, growth factors, and electrophysiology. This revealed categorical differences in the kinds of genes regulated in HVC and RA. These results show that different molecular programs underlie seasonal changes in HVC and RA, and that gene expression is time specific across different reproductive conditions. Our results provide insights into the complex molecular pathways that underlie adult neural plasticity

Selecting CMIP5 GCMs for downscaling over multiple regions

The unprecedented availability of 6-hourly data from a multi-model GCM ensemble in the CMIP5 data archive presents the new opportunity to dynamically downscale multiple GCMs to develop high-resolution climate projections relevant to detailed assessment of climate vulnerability and climate change impacts. This enables the development of high resolution projections derived from the same set of models that are used to characterise the range of future climate changes at the global and large-scale, and as assessed in the IPCC AR5. However, the technical and human resource required to dynamically-downscale the full CMIP5 ensemble are significant and not necessary if the aim is to develop scenarios covering a representative range of future climate conditions relevant to a climate change risk assessment. This paper illustrates a methodology for selecting from the available CMIP5 models in order to identify a set of 8–10 GCMs for use in regional climate change assessments. The selection focuses on their suitability across multiple regions—Southeast Asia, Europe and Africa. The selection (a) avoids the inclusion of the least realistic models for each region and (b) simultaneously captures the maximum possible range of changes in surface temperature and precipitation for three continental-scale regions. We find that, of the CMIP5 GCMs with 6-hourly fields available, three simulate the key regional aspects of climate sufficiently poorly that we consider the projections from those models ‘implausible’ (MIROC-ESM, MIROC-ESM-CHEM, and IPSL-CM5B-LR). From the remaining models, we demonstrate a selection methodology which avoids the poorest models by including them in the set only if their exclusion would significantly reduce the range of projections sampled. The result of this process is a set of models suitable for using to generate downscaled climate change information for a consistent multi-regional assessment of climate change impacts and adaptation

Effect of Global Cardiac Ischemia on Human Ventricular Fibrillation: Insights from a Multi-scale Mechanistic Model of the Human Heart

Acute regional ischemia in the heart can lead to cardiac arrhythmias such as ventricular fibrillation (VF), which in turn compromise cardiac output and result in secondary global cardiac ischemia. The secondary ischemia may influence the underlying arrhythmia mechanism. A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF. During 150 seconds of global ischemia the dominant frequency of activation decreased, while after reperfusion it increased rapidly. At the same time the complexity of epicardial excitation, measured as the number of epicardical phase singularity points, remained approximately constant during ischemia. Here we perform numerical studies based on these clinical data and propose explanations for the observed dynamics of the period and complexity of activation patterns. In particular, we study the effects on ischemia in pseudo-1D and 2D cardiac tissue models as well as in an anatomically accurate model of human heart ventricles. We demonstrate that the fall of dominant frequency in VF during secondary ischemia can be explained by an increase in extracellular potassium, while the increase during reperfusion is consistent with washout of potassium and continued activation of the ATP-dependent potassium channels. We also suggest that memory effects are responsible for the observed complexity dynamics. In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements

WNT signalling in prostate cancer

Genome sequencing and gene expression analyses of prostate tumours have highlighted the potential importance of genetic and epigenetic changes observed in WNT signalling pathway components in prostate tumours-particularly in the development of castration-resistant prostate cancer. WNT signalling is also important in the prostate tumour microenvironment, in which WNT proteins secreted by the tumour stroma promote resistance to therapy, and in prostate cancer stem or progenitor cells, in which WNT-β-catenin signals promote self-renewal or expansion. Preclinical studies have demonstrated the potential of inhibitors that target WNT receptor complexes at the cell membrane or that block the interaction of β-catenin with lymphoid enhancer-binding factor 1 and the androgen receptor, in preventing prostate cancer progression. Some WNT signalling inhibitors are in phase I trials, but they have yet to be tested in patients with prostate cancer