3,030 research outputs found
A life worth writing about
Craig Venter's autobiography recounts the conflict and controversy that have contributed to his celebrity
Vascular miR‐181b controls tissue factor‐dependent thrombogenicity and inflammation in type 2 diabetes
BACKGROUND:
Diabetes mellitus is characterized by chronic vascular inflammation leading to pathological expression of the thrombogenic full length (fl) tissue factor (TF) and its isoform alternatively-spliced (as) TF. Blood-borne TF promotes factor (F) Xa generation resulting in a pro-thrombotic state and cardiovascular complications. MicroRNA (miR)s impact gene expression on the post-transcriptional level and contribute to vascular homeostasis. Their distinct role in the control of the diabetes-related procoagulant state remains poorly understood.
METHODS:
In a cohort of patients with poorly controlled type 2 diabetes (n = 46) plasma levels of miR-181b were correlated with TF pathway activity and markers for vascular inflammation. In vitro, human microvascular endothelial cells (HMEC)-1 and human monocytes (THP-1) were transfected with miR-181b or anti-miR-181b and exposed to tumor necrosis factor (TNF) α or lipopolysaccharides (LPS). Expression of TF isoforms, vascular adhesion molecule (VCAM) 1 and nuclear factor (NF) κB nuclear translocation was assessed. Moreover, aortas, spleen, plasma, and bone marrow-derived macrophage (BMDM)s of mice carrying a deletion of the first miR-181b locus were analyzed with respect to TF expression and activity.
RESULTS:
In patients with type 2 diabetes, plasma miR-181b negatively correlated with the procoagulant state as evidenced by TF protein, TF activity, D-dimer levels as well as markers for vascular inflammation. In HMEC-1, miR-181b abrogated TNFα-induced expression of flTF, asTF, and VCAM1. These results were validated using the anti-miR-181b. Mechanistically, we confirmed a miR-181b-mediated inhibition of importin-α3 (KPNA4) leading to reduced nuclear translocation of the TF transcription factor NFκB. In THP-1, miR-181b reduced both TF isoforms and FXa generation in response to LPS due to targeting phosphatase and tensin homolog (PTEN), a principal inducer for TF in monocytes. Moreover, in miR-181-/- animals, we found that reduced levels of miR-181b were accompanied by increased TF, VCAM1, and KPNA4 expression in aortic tissue as well as increased TF and PTEN expression in spleen. Finally, BMDMs of miR-181-/- mice showed increased TF expression and FXa generation upon stimulation with LPS.
CONCLUSIONS:
miR-181b epigenetically controls the procoagulant state in diabetes. Reduced miR-181b levels contribute to increased thrombogenicity and may help to identify individuals at particular risk for thrombosis
Current challenges in de novo plant genome sequencing and assembly
ABSTRACT: Genome sequencing is now affordable, but assembling plant genomes de novo remains challenging. We assess the state of the art of assembly and review the best practices for the community
Two unusual silicoflagellate double skeletons
A study of silicoflagellate double skeletons revealed two unusual doublets that are illustrated and discussed here. One of these comprises two ten-sided Octactis skeletons that appear to form a doublet, but both in the same (apical) orientation. The other specimen is a double skeleton of Dictyocha
that is slightly disarticulated, with a third, less robust skeleton in between. These unusual double skeletons suggest that there is much more to be learned about the formation of silicoflagellate skeletons and the reproductive processes in this protist grou
Analysis and calibration of absorptive images of Bose-Einstein condensate at non-zero temperatures
We describe the method allowing quantitative interpretation of absorptive
images of mixtures of BEC and thermal atoms which reduces possible systematic
errors associated with evaluation of the contribution of each fraction. By
using known temperature dependence of the BEC fraction, the analysis allows
precise calibration of the fitting results. The developed method is verified in
two different measurements and compares well with theoretical calculations and
with measurements performed by another group.Comment: 17 pages, 8 figure
GUARDIANS final report part 1 (draft): a robot swarm assisting a human fire fighter
Emergencies in industrial warehouses are a major concern for fire fighters. The large dimensions together with the development of dense smoke that drastically reduces visibility, represent major challenges. The Guardians robot swarm is designed to assist re ghters in searching a
large warehouse. In this paper we discuss the technology developed for a swarm of robots assisting re ghters. We explain the swarming algorithms which provide the functionality by which the robots react to and follow humans while no communication is required. Next we discuss the wireless communication system, which is a so-called mobile ad-hoc network. The communication network provides also the means to locate the robots and humans. Thus the robot swarm is able to provide guidance information to the humans. Together with the fire fighters we explored how
the robot swarm should feed information back to the human fire fighter. We have designed and experimented with interfaces for presenting swarm based information to human beings
The thermo-oxidative degradation of poly(4-methylstyrene) and its relationship to flammability
Polystyrene and poly(4-methylstyrene) have very similar chemical structures with the only differences being the para methyl group of poly(4-methylstyrene). This methyl group is susceptible to oxidation at elevated temperatures. Here we demonstrate that it is possible to introduce oxidative cross-links to poly(4-methylstyrene), via the para methyl group, by thermal oxidative treatment at 230 °C, 250 °C and 270 °C in the absence of catalyst, leading to a material with markedly modified thermal degradation chemistry. Thermal gravimetric analysis and differential scanning calorimetry were used to characterise and compare untreated and post-oxidised materials and established that as the temperature of pre-treatment was increased, the subsequent thermal stability of the material increased. FTIR, NMR and microanalysis indicated that after the thermal oxidative pre-treatment ether cross-links are present alongside new oxygen containing functional groups such as aldehydes, carboxylic acids and hydroxyl groups. Finally, data obtained from pyrolysis combustion flow calorimetry confirmed that as the number of oxidative cross-links increase, a reduction in the polymer's flammability as assessed by heat release data is observed
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