miR-718 represses proinflammatory cytokine production through targeting phosphatase and tensin homolog (PTEN)

Bacterial sepsis involves a complex interaction between the host immune response and bacterial LPS. LPS binds Toll-like receptor (TLR) 4, which leads to the release of proinflammatory cytokines that are essential for a potent innate immune response against pathogens. The innate immune system is tightly regulated, as excessive inflammation can lead to organ failure and death. MicroRNAs have recently emerged as important regulators of the innate immune system. Here we determined the function of miR-718, which is conserved across mammals and overlaps with the 5\u27 UTR of the interleukin 1 receptor-associated kinase (IRAK1) gene. As IRAK1 is a key component of innate immune signaling pathways that are downstream of most TLRs, we hypothesized that miR-718 helps regulate the innate immune response. Activation of TLR4, but not TLR3, induced the expression of miR-718 in macrophages. miR-718 expression was also induced in the spleens of mice upon LPS injection. miR-718 modulates PI3K/Akt signaling by directly down-regulating phosphatase and tensin homolog (PTEN), thereby promoting phosphorylation of Akt, which leads to a decrease in proinflammatory cytokine production. Phosphorylated Akt induces let-7e expression, which, in turn, down-regulates TLR4 and further diminishes TLR4-mediated proinflammatory signals. Decreased miR-718 expression is associated with bacterial burden during Neisseria gonorrhoeae infection and alters the infection dynamics of N. gonorrhoeae in vitro Furthermore, miR-718 regulates the induction of LPS tolerance in macrophages. We propose a role for miR-718 in controlling TLR4 signaling and inflammatory cytokine signaling through a negative feedback regulation loop involving down-regulation of TLR4, IRAK1, and NF-kappaB

A New Solution to the Relative Orientation Problem using only 3 Points and the Vertical Direction

This paper presents a new method to recover the relative pose between two images, using three points and the vertical direction information. The vertical direction can be determined in two ways: 1- using direct physical measurement like IMU (inertial measurement unit), 2- using vertical vanishing point. This knowledge of the vertical direction solves 2 unknowns among the 3 parameters of the relative rotation, so that only 3 homologous points are requested to position a couple of images. Rewriting the coplanarity equations leads to a simpler solution. The remaining unknowns resolution is performed by an algebraic method using Grobner bases. The elements necessary to build a specific algebraic solver are given in this paper, allowing for a real-time implementation. The results on real and synthetic data show the efficiency of this method

First measurements of the analyzing powers of the proton-deuteron break-up reaction at large proton scattering angles

A measurement of the analyzing powers for the 2H(p, pp )n break-up reaction was carried out at KVI exploiting a polarized-proton beam at 135 MeV. In this work, we extended the earlier measurements that were done for kinematical configurations at small proton scattering angles to large angles. The results are compared with theoretical calculations based on a two-nucleon (NN) potential alone or combined with a three-nucleon (3N) potential. The theoretical calculations describe the main features of the measured distributions, but none of them can reproduce the details. This indicates the need for further development of the 3N force models

Differential Methylation of the HPV 16 Upstream Regulatory Region during Epithelial Differentiation and Neoplastic Transformation

High risk human papillomaviruses are squamous epitheliotropic viruses that may cause cervical and other cancers. HPV replication depends on squamous epithelial differentiation. Transformation of HPV-infected cells goes along with substantial alteration of the viral gene expression profile and preferentially occurs at transformation zones usually at the uterine cervix. Methylation of the viral genome may affect regulatory features that control transcription and replication of the viral genome. Therefore, we analyzed the methylation pattern of the HPV16 upstream regulatory region (URR) during squamous epithelial differentiation and neoplastic transformation and analyzed how shifts in the HPV URR methylome may affect viral gene expression and replication. HPV 16 positive biopsy sections encompassing all stages of an HPV infection (latent, permissive and transforming) were micro-dissected and DNA was isolated from cell fractions representing the basal, intermediate, and superficial cell layers, each, as well as from transformed p16INK4a-positive cells. We observed fundamental changes in the methylation profile of transcription factor binding sites in the HPV16 upstream regulatory region linked to the squamous epithelial differentiation stage. Squamous epithelial transformation indicated by p16INK4a overexpression was associated with methylation of the distal E2 binding site 1 leading to hyper-activation of the HPV 16 URR. Adjacent normal but HPV 16-infected epithelial areas retained hyper-methylated HPV DNA suggesting that these viral genomes were inactivated. These data suggest that distinct shifts of the HPV 16 methylome are linked to differentiation dependent transcription and replication control and may trigger neoplastic transformation

Psychosocial factors associated with the self-reported frequency of cell phone use while driving in Iran

Cell phone use while driving is a common contributing factor in thousands of road traffic injuries every year globally. Despite extensive research investigating the risks associated with cell phone use while driving, social media campaigns to raise public awareness and a number of laws banning phone use while driving, this behaviour remains prevalent throughout the world. The current study was conducted in Iran, where road traffic injuries are the leading causes of death and disability, and where drivers continue to use their cell phones, despite legislative bans restricting this behaviour. A total of 255 drivers in the city of Mashhad (male = 66.3%; mean age = 30.73 years; SD = 9.89) completed either an online or a paper-based survey assessing the self-reported frequency of using a cell phone while driving. Psychosocial factors contributing to cell phone use while driving and support for legislation restricting this behaviour, as well as the Big Five personality traits, were also measured. Overall, the results showed that almost 93% of drivers use their cell phones while driving at least once a week, with 32.5% reporting they always use their cell phones while driving. Ordinal logistic regression revealed that the presence of a child passenger, age, perceived benefits and risks of using cell phones while driving, as well as the perceived ability to drive safely while using a cell phone, were strongly associated with the frequency of cell phone use while driving. As for personality traits—extraversion, agreeableness and conscientiousness significantly predicted the frequency of cell phone use in this sample of Iranian drivers

Nuclear force studies in the proton-deuteron break-up channel at 135 MeV

In this contribution, vector analyzing powers, Ax and Ay, are presented for the proton-deuteron break-up reaction studied using a polarised-proton beam at 135 MeV impinging on a liquid-deuterium target. For the experiment we used the Big Instrument for Nuclear-polarisation Analysis (BINA) at KVI, the Netherlands. With this setup, we expanded our measurements of analyzing powers compared to earlier published result (Kalantar-Nayestanaki N. et al., Rep. Prog. Phys. 75 (2012)). In particular, we determined, for the first time, Ax for a large range in the kinematical S, polar and azimuthal angles of the two outgoing protons. Analyzing power data are compared to predictions from Faddeev calculations. Our data are reasonably well described by calculations for kinematical configurations at which the three-nucleon force effect is predicted to be small. However, striking discrepancies are observed at specific configurations, in particular in cases where the relative azimuthal angle between the two protons becomes small. In this contribution, some of these configurations along with the analysis techniques will be presented

Evolution and resolution of brain involvement associated with SARS- CoV2 infection: A close Clinical � Paraclinical follow up study of a case

The new severe acute respiratory syndrome- coronavirus 2 is reported to affect the nervous system. Among the reports of the various neurological manifestations, there are a few documented specific processes to explain the neurological signs. We report a para-infectious encephalitis patient with clinical, laboratory, and imaging findings during evolution and convalescence phase of coronavirus infection. This comprehensive overview can illuminate the natural history of similar cases. As the two previously reported cases of encephalitis associated with this virus were not widely discussed regarding the treatment, we share our successful approach and add some recommendations about this new and scarce entity. © 2020 Elsevier B.V

CD36 coordinates NLRP3 inflammasome activation by facilitating the intracellular nucleation from soluble to particulate ligands in sterile inflammation

Particulate ligands including cholesterol crystals and amyloid fibrils induce NLRP3-dependent production of interleukin-1β (IL-1β) in atherosclerosis, Alzheimer's disease and diabetes. Soluble endogenous ligands including oxidized-LDL, amyloid-β and amylin peptides accumulate in these diseases. Here we identify a CD36-mediated endocytic pathway that coordinates the intracellular conversion of these soluble ligands to crystals or fibrils, resulting in lysosomal disruption and NLRP3-inflammasome activation. Consequently, macrophages lacking CD36 failed to elicit IL-1β production in response to these ligands and targeting CD36 in atherosclerotic mice reduced serum IL-1β and plaque cholesterol crystal accumulation. Collectively, these findings highlight the importance of CD36 in the accrual and nucleation of NLRP3 ligands from within the macrophage and position CD36 as a central regulator of inflammasome activation in sterile inflammation