Epigenomic mechanisms regulate distinct aspects of the inflammatory response in immune cells. Despite the central role for microglia in neuroinflammation and neurodegeneration, little is known about ...their epigenomic regulation of the inflammatory response. Here, we show that Ten-eleven translocation 2 (TET2) methylcytosine dioxygenase expression is increased in microglia upon stimulation with various inflammogens through a NF-κB-dependent pathway. We found that TET2 regulates early gene transcriptional changes, leading to early metabolic alterations, as well as a later inflammatory response independently of its enzymatic activity. We further show that TET2 regulates the proinflammatory response in microglia of mice intraperitoneally injected with LPS. We observed that microglia associated with amyloid β plaques expressed TET2 in brain tissue from individuals with Alzheimer’s disease (AD) and in 5xFAD mice. Collectively, our findings show that TET2 plays an important role in the microglial inflammatory response and suggest TET2 as a potential target to combat neurodegenerative brain disorders.
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•TET2 is upregulated in microglia cells upon various inflammatory stimuli•TET2 regulates TLR-4-induced type I IFN response and LPS-induced aerobic glycolysis•TET2 regulates the proinflammatory response induced by LPS in vitro and in vivo•TET2 is expressed by amyloid β plaque-associated microglia in AD brains
Microglia play a key role in neuroinflammation and neurodegeneration in different neurodegenerative diseases, but little is known about the epigenetic modifying enzymes regulating their inflammatory response. Carrillo-Jimenez et al. identify TET2 as a major regulator of the microglia proinflammatory response and suggest that, by targeting this protein, microglial activation could be impaired.
The existence of multiple subclasses of Type Ia supernovae (SNe Ia) has been the subject of great debate in the last decade. One major challenge inevitably met when trying to infer the existence of ...one or more subclasses is the time consuming, and subjective, process of subclass definition. In this work, we show how machine learning tools facilitate identification of subtypes of SNe Ia through the establishment of a hierarchical group structure in the continuous space of spectral diversity formed by these objects. Using deep learning, we were capable of performing such identification in a four-dimensional feature space (+1 for time evolution), while the standard principal component analysis barely achieves similar results using 15 principal components. This is evidence that the progenitor system and the explosion mechanism can be described by a small number of initial physical parameters. As a proof of concept, we show that our results are in close agreement with a previously suggested classification scheme and that our proposed method can grasp the main spectral features behind the definition of such subtypes. This allows the confirmation of the velocity of lines as a first-order effect in the determination of SN Ia subtypes, followed by 91bg-like events. Given the expected data deluge in the forthcoming years, our proposed approach is essential to allow a quick and statistically coherent identification of SNe Ia subtypes (and outliers). All tools used in this work were made publicly available in the python package Dimensionality Reduction And Clustering for Unsupervised Learning in Astronomy (dracula) and can be found within COINtoolbox (https://github.com/COINtoolbox/DRACULA).
Osteosarcoma is the most prevalent primary pediatric cancer-related bone disease. These tumors frequently develop resistance to chemotherapy and are highly metastatic, leading to poor outcome. Thus, ...there is a need for new therapeutic strategies that can prevent cell dissemination. We previously showed that CYR61/CCN1 expression in osteosarcoma cells is correlated to aggressiveness both in vitro and in vivo in mouse models, as well as in patients. In this study, we found that CYR61 is a critical contributor to the vascularization of primary tumor. We demonstrate that silencing CYR61, using lentiviral transduction, leads to a significant reduction in expression level of pro-angiogenic markers such as VEGF, FGF2, PECAM and angiopoietins concomitantly to an increased expression of major anti-angiogenic markers such as thrombospondin-1 and SPARC. Matrix metalloproteinase-2 family member expression, a key pathway in osteosarcoma metastatic capacity was also downregulated when CYR61 was downregulated in osteosarcoma cells. Using a metastatic murine model, we show that CYR61 silencing in osteosarcoma cells results in reduced tumor vasculature and slows tumor growth compared with control. We also find that microvessel density correlates with lung metastasis occurrence and that CYR61 silencing in osteosarcoma cells limits the number of metastases. Taken together, our data indicate that CYR61 silencing can blunt the malignant behavior of osteosarcoma tumor cells by limiting primary tumor growth and dissemination process.
Claims surrounding exceptional longevity are sometimes disputed or dismissed for lack of credible evidence. Here, we present three DNA methylation-based age estimators (epigenetic clocks) for ...verifying age claims of centenarians. The three centenarian clocks were developed based on
n
= 7039 blood and saliva samples from individuals older than 40, including
n
= 184 samples from centenarians, 122 samples from semi-supercentenarians (aged 105 +), and 25 samples from supercentenarians (aged 110 +). The oldest individual was 115 years old. Our most accurate centenarian clock resulted from applying a neural network model to a training set composed of individuals older than 40. An epigenome-wide association study of age in different age groups revealed that age effects in young individuals (age < 40) are correlated (
r
= 0.55) with age effects in old individuals (age > 90). We present a chromatin state analysis of age effects in centenarians. The centenarian clocks are expected to be useful for validating claims surrounding exceptional old age.
Aims: To evaluate spoilage and identify lactic acid bacteria (LAB) from spoilage associations of cooked and brined shrimps stored under modified atmosphere packaging (MAP) at 0, 5, 8, 15 and 25°C.
...Methods and Results: Bacterial isolates (102) from spoilage associations of cooked and brined MAP shrimps were characterized by phenotypic tests and identified as lactic acid bacteria (78 isolates), other Gram‐positive bacteria (13 isolates) and Gram‐negative bacteria (11 isolates). A selection of 48 LAB isolates were further characterized and identified by phenotypic tests and SDS‐PAGE electrophoresis of whole cell proteins. Selected clusters of LAB isolates were analysed by plasmid profiling, pulsed field gel electrophoresis and 16S rRNA gene sequencing. Enterococcus faecalis was identified in spoilage associations at 15°C and 25°C, and its metabolic activity corresponded to chemical changes in spoiled products. Carnobacterium divergens, a non‐motile Carnobacterium sp. nov. and Lactobacillus curvatus were the LAB species observed in spoilage associations of products stored at 0°C, 5°C and 8°C.
Conclusions:
Enterococcus spp. and Carnobacterium spp. were the dominant parts of spoilage associations of cooked and brined MAP shrimps stored at high and low temperatures, respectively.
Significance and Impact of the Study: The SDS‐PAGE technique and simple biochemical keys allowed the majority of LAB isolates from spoilage associations of cooked and brined MAP shrimps to be identified at the species level.
We describe the development of cross-correlation based high resolution electron backscatter diffraction (HR-EBSD) and electron channelling contrast imaging (ECCI), in the scanning electron microscope ...(SEM), to quantitatively map the strain variation and lattice rotation and determine the density and identify dislocations in nitride semiconductor thin films. These techniques can provide quantitative, rapid, non-destructive analysis of the structural properties of materials with a spatial resolution of order of tens of nanometers. HR-EBSD has a sensitivity to changes of strain and rotation of the order of 10−4 and 0.01° respectively, while ECCI can be used to image single dislocations up to a dislocation density of order 1010 cm−2. In the present work, we report the application of the cross-correlation based HR-EBSD approach to determine the tilt, twist, elastic strain and the distribution and type of threading dislocations in InAlN/AlN/GaN high electron mobility transistor (HEMT) structures grown on two different substrates, namely SiC and sapphire. We describe our procedure to estimate the distribution of geometrically necessary dislocations (GND) based on Nye-Kroner analysis and compare them with the direct imaging of threading dislocations (TDs) by ECCI. Combining data from HR-EBSD and ECCI observations allowed the densities of pure edge, mixed and pure screw threading dislocations to be fully separated.
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Optical properties of InN grown on Si(111) substrate Sakalauskas, E.; Schley, P.; Räthel, J. ...
Physica status solidi. A, Applications and materials science,
20/May , Letnik:
207, Številka:
5
Journal Article, Conference Proceeding
Recenzirano
A comprehensive characterization of the optical properties of wurtzite InN films grown by molecular beam epitaxy on Si(111) substrates is presented. Two types of films are investigated in this work: ...InN on AlN/Si(111) and InN on GaN/AlN/Si(111). Their properties are compared to a layer deposited on GaN/sapphire substrate. The dielectric function (DF) is obtained from spectroscopic ellipsometry (SE). The infrared studies yield the plasma frequency and thus the electron density, while the interband absorption is probed between 0.56 and 9.8 eV. For InN grown on Si(111) substrate, the absorption onset is slightly shifted to higher energies with respect to the InN film grown on GaN/sapphire which can be attributed to higher electron concentrations. Despite this, strongly pronounced optical transitions due to critical points of the band structure are found in the high‐energy part of the DF. It emphasizes the already promising quality of the InN films on silicon. Band‐gap renormalization (BGR), band filling, and strain are taken into account in order to estimate the intrinsic band gap of wurtzite InN. For the InN layers on silicon, we get a band gap between 0.66 and 0.685 eV.
Over the past 70 years, heat has been widely used as a tracer for estimating the flow of water in woody and herbaceous plants. However, most commercially available techniques for monitoring whole ...plant water use are invasive and the measurements are potentially flawed because of wounding of the xylem tissue. The study of photosynthate transport in the phloem remains in its infancy, and little information about phloem transport rates is available owing to the fragility of the vascular tissue. The aim of our study was to develop a compact, stand-alone non-invasive system allowing for direct detection of phloem and xylem sap movement. The proposed method uses a heat pulse as a tracer for sap flow. Heat is applied to the surface of the stem with a near-infrared laser source, and heat propagation is monitored externally by means of an infrared camera. Heat pulse velocities are determined from the thermometric data and related to the more useful quantity, mass flow rate. Simulation experiments on the xylem tissue of severed silver birch (Betula pendula Roth.) branch segments were performed to assess the feasibility of the proposed approach, highlight the characteristics of the technique and outline calibration strategies. Good agreement between imposed and measured flow rates was achieved leading to experimentation with live silver birch and oak (Quercus robur L.) saplings. It was demonstrated that water flow through xylem vessels can be monitored non-invasively on an intact stem with satisfactory accuracy despite simultaneous sugar transport in the phloem. In addition, it was demonstrated that the technique allows for unequivocal detection of phloem flow velocities.
We experimentally demonstrate a 5G digital fronthaul network that relies on multi-adaptive bandwidth/bitrate variable transceivers (BVTs) and an autonomic software-defined networking (SDN) control ...system for partially-disaggregated wavelength division multiplexing (WDM)/space division multiplexing (SDM). Transmission of 256-QAM 760.32 MHz orthogonal frequency-division multiplexing (OFDM) radio signal is performed, with a total radio transmission capacity of 5.667 Gb/s. Digitized signal samples are carried as a 22.25 Gb/s digitized radio-over-fiber (DRoF) data stream and transmitted over a WDM/SDM infrastructure including 40-wavelength 100-GHz arrayed waveguide gratings (AWGs) and 19-core fiber. The autonomic SDN controller deploys a control loop for the multi-adaptive OFDM-based BVTs that monitors the per-subcarrier signal to noise ratio (SNR) and assigns the optimal constellation based on the actual signal degradation. An error vector magnitude (EVM) below the targeted 2.1% is achieved while setting up connections in less than 5 s.
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