Novel insights into the cardio-protective effects of FGF21 in lean and obese rat hearts

Aims: Fibroblast growth factor 21 (FGF21) is a hepatic metabolic regulator with pleotropic actions. Its plasma concentrations are increased in obesity and diabetes; states associated with an increased incidence of cardiovascular disease. We therefore investigated the direct effect of FGF21 on cardio-protection in obese and lean hearts in response to ischemia. Methods and Results: FGF21, FGF21-receptor 1 (FGFR1) and beta-Klotho (βKlotho) were expressed in rodent, human hearts and primary rat cardiomyocytes. Cardiac FGF21 was expressed and secreted (real time RT-PCR/western blot and ELISA) in an autocrine-paracrine manner, in response to obesity and hypoxia, involving FGFR1-βKlotho components. Cardiac-FGF21 expression and secretion were increased in response to global ischemia. In contrast βKlotho was reduced in obese hearts. In isolated adult rat cardiomyocytes, FGF21 activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt), ERK1/2(extracellular signal-regulated kinase) and AMPK (AMP-activated protein kinase) pathways. In Langendorff perfused rat [adult male wild-type wistar] hearts, FGF21 administration induced significant cardio-protection and restoration of function following global ischemia. Inhibition of PI3K/Akt, AMPK, ERK1/2 and ROR-α (retinoic-acid receptor alpha) pathway led to significant decrease of FGF21 induced cardio-protection and restoration of cardiac function in response to global ischemia. More importantly, this cardio-protective response induced by FGF21 was reduced in obesity, although the cardiac expression profiles and circulating FGF21 levels were increased. Conclusion: In an ex vivo Langendorff system, we show that FGF21 induced cardiac protection and restoration of cardiac function involving autocrine-paracrine pathways, with reduced effect in obesity. Collectively, our findings provide novel insights into FGF21-induced cardiac effects in obesity and ischemia

The effect of utilizing silica fume and eggshell ash on the geotechnical properties of soft kaolin clay

The application of chemical stabilizer in soil stabilization can effectively reduce the negative environmental impact in the construction industry. However, the stabilization of soft clay remains a challenge due to the costly and non-eco-friendly materials such as cement and lime. This research demonstrates the combination of SF and ESA in stabilizing the kaolin soils, based on the basic engineering properties and undrained shear strength (USS). Its effect was studied via the inclusion as cement replacement material in kaolin soil at 2, 4 and 6% (by weight of dry soft kaolin clay soil) of SF and ESA substitutions of 3, 6 and 9% (by weight of dry soft kaolin clay and SF content). The result shows a considerably lower specific gravity (4.9% reduction), reduced plasticity index (PI)(48.4% reduction), decreased maximum dry density (MDD) (5.5% reduction), increased optimum moisture content (OMC)(8.7% increment), and higher USS (68.8%). In conclusion, the combinations of SF and ESA as soil stabilization agents successfully enhance the soil strength of the kaolin opening a route to the low cost and eco-friendly materials in soil stabilization

The role of HLA-G in human pregnancy

Pregnancy in mammals featuring hemochorial placentation introduces a major conflict with the mother's immune system, which is dedicated to repelling invaders bearing foreign DNA and RNA. Numerous and highly sophisticated strategies for preventing mothers from rejecting their genetically different fetus(es) have now been identified. These involve production of novel soluble and membrane-bound molecules by uterine and placental cells. In humans, the placenta-derived molecules include glycoproteins derived from the HLA class Ib gene, HLA-G. Isoforms of HLA-G saturate the maternal-fetal interface and circulate in mothers throughout pregnancy. Uteroplacental immune privilege for the fetus and its associated tissues is believed to result when immune cells encounter HLA-G. Unequivocally demonstration of this concept requires experiments in animal models. Both the monkey and the baboon express molecules that are similar but not identical to HLA-G, and may comprise suitable animal models for establishing a central role for these proteins in pregnancy

Improvement of Sidestream Dark Field Imaging with an Image Acquisition Stabilizer

Background: In the present study we developed, evaluated in volunteers, and clinically validated an image acquisition stabilizer (IAS) for Sidestream Dark Field (SDF) imaging.Methods: The IAS is a stainless steel sterilizable ring which fits around the SDF probe tip. The IAS creates adhesion to the imaged tissue by application of negative pressure. The effects of the IAS on the sublingual microcirculatory flow velocities, the force required to induce pressure artifacts (PA), the time to acquire a stable image, and the duration of stable imaging were assessed in healthy volunteers. To demonstrate the clinical applicability of the SDF setup in combination with the IAS, simultaneous bilateral sublingual imaging of the microcirculation were performed during a lung recruitment maneuver (LRM) in mechanically ventilated critically ill patients. One SDF device was operated handheld; the second was fitted with the IAS and held in position by a mechanic arm. Lateral drift, number of losses of image stability and duration of stable imaging of the two methods were compared.Results: Five healthy volunteers were studied. The IAS did not affect microcirculatory flow velocities. A significantly greater force had to applied onto the tissue to induced PA with compared to without IAS (0.25 ± 0.15 N without vs. 0.62 ± 0.05 N with the IAS, p < 0.001). The IAS ensured an increased duration of a stable image sequence (8 ± 2 s without vs. 42 ± 8 s with the IAS, p < 0.001). The time required to obtain a stable image sequence was similar with and without the IAS. In eight mechanically ventilated patients undergoing a LRM the use of the IAS resulted in a significantly reduced image drifting and enabled the acquisition of significantly longer stable image sequences (24 ± 5 s without vs. 67 ± 14 s with the IAS, p = 0.006).Conclusions: The present study has validated the use of an IAS for improvement of SDF imaging by demonstrating that the IAS did not affect microcirculatory perfusion in the microscopic field of view. The IAS improved both axial and lateral SDF image stability and thereby increased the critical force required to induce pressure artifacts. The IAS ensured a significantly increased duration of maintaining a stable image sequence

Network-Based Pipeline for Analyzing MS Data: An Application toward Liver Cancer

10.1021/pr1010845Journal of Proteome Research1052261-2272JPRO

Self‐Assembled Surfactant‐Polyoxovanadate Soft Materials as Tuneable Vanadium Oxide Cathode Precursors for Lithium‐Ion Batteries

The mixing of [V10O28]6− decavanadate anions with a dicationic gemini surfactant (gem) leads to the spontaneous self-assembly of surfactant-templated nanostructured arrays of decavanadate clusters. Calcination of the material under air yields highly crystalline, sponge-like V2O5 (gem-V2O5). In contrast, calcination of the amorphous tetrabutylammonium decavanadate allows isolation of a more agglomerated V2O5 consisting of very small crystallites (TBA-V2O5). Electrochemical analysis of the materials’ performance as lithium-ion intercalation electrodes highlights the role of morphology in cathode performance. The large crystallites and long-range microstructure of the gem-V2O5 cathode deliver higher initial capacity and superior capacity retention than TBA-V2O5. The smaller crystallite size and higher surface area of TBA-V2O5 allow faster lithium insertion and superior rate performance to gem-V2O5

Studies on the virome of the entomopathogenic fungus Beauveria bassiana reveal novel dsRNA elements and mild hypervirulence.

© 2017 Kotta-Loizou, Coutts. 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. Kotta-Loizou I, Coutts RHA (2017) 'Studies on the Virome of the Entomopathogenic Fungus Beauveria bassiana Reveal Novel dsRNA Elements and Mild Hypervirulence', PLoS Pathogens, 13(1): e1006183. doi:10.1371/journal.ppat.1006183The entomopathogenic fungus Beauveria bassiana has a wide host range and is used as a biocontrol agent against arthropod pests. Mycoviruses have been described in phytopathogenic fungi while in entomopathogenic fungi their presence has been reported only rarely. Here we show that 21.3% of a collection of B. bassiana isolates sourced from worldwide locations, harbor dsRNA elements. Molecular characterization of these elements revealed the prevalence of mycoviruses belonging to the Partitiviridae and Totiviridae families, the smallest reported virus to date, belonging to the family Narnaviridae, and viruses unassigned to a family or genus. Of particular importance is the discovery of members of a newly proposed family Polymycoviridae in B. bassiana. Polymycoviruses, previously designated as tetramycoviruses, consist of four non-conventionally encapsidated capped dsRNAs. The presence of additional non-homologous genomic segments in B. bassiana polymycoviruses and other fungi illustrates the unprecedented dynamic nature of the viral genome. Finally, a comparison of virus-free and virus-infected isogenic lines derived from an exemplar B. bassiana isolate revealed a mild hypervirulent effect of mycoviruses on the growth of their host isolate and on its pathogenicity against the greater wax moth Galleria mellonella, highlighting for the first time the potential of mycoviruses as enhancers of biocontrol agents.Peer reviewedFinal Published versio

Robust simplifications of multiscale biochemical networks

<p>Abstract</p> <p>Background</p> <p>Cellular processes such as metabolism, decision making in development and differentiation, signalling, etc., can be modeled as large networks of biochemical reactions. In order to understand the functioning of these systems, there is a strong need for general model reduction techniques allowing to simplify models without loosing their main properties. In systems biology we also need to compare models or to couple them as parts of larger models. In these situations reduction to a common level of complexity is needed.</p> <p>Results</p> <p>We propose a systematic treatment of model reduction of multiscale biochemical networks. First, we consider linear kinetic models, which appear as "pseudo-monomolecular" subsystems of multiscale nonlinear reaction networks. For such linear models, we propose a reduction algorithm which is based on a generalized theory of the limiting step that we have developed in <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Second, for non-linear systems we develop an algorithm based on dominant solutions of quasi-stationarity equations. For oscillating systems, quasi-stationarity and averaging are combined to eliminate time scales much faster and much slower than the period of the oscillations. In all cases, we obtain robust simplifications and also identify the critical parameters of the model. The methods are demonstrated for simple examples and for a more complex model of NF-<it>κ</it>B pathway.</p> <p>Conclusion</p> <p>Our approach allows critical parameter identification and produces hierarchies of models. Hierarchical modeling is important in "middle-out" approaches when there is need to zoom in and out several levels of complexity. Critical parameter identification is an important issue in systems biology with potential applications to biological control and therapeutics. Our approach also deals naturally with the presence of multiple time scales, which is a general property of systems biology models.</p