Human tribbles-1 controls proliferation and chemotaxis of smooth muscle cells via MAPK signaling pathways

Migration and proliferation of smooth muscle cells are key to a number of physiological and pathological processes, including wound healing and the narrowing of the vessel wall.Previous work has shown links between inflammatory stimuli and vascular smooth muscle cell proliferation and migration through mitogen activated protein kinase (MAPK) activation, though the molecular mechanisms of this process are poorly understood. Here we report that tribbles-1, a recently described modulator of MAPK activation controls vascular smooth muscle cell proliferation and chemotaxis via the Jun Kinase pathway. Our findings demonstrate that this regulation takes place via direct interactions between tribbles-1 and MKK4/SEK1, a Jun activator kinase. The activity of this kinase is dependent on tribbles-1 levels, whilst the activation and the expression of MKK4/SEK1 is not. In addition, tribbles-1 expression is elevated in human atherosclerotic arteries compared to non-atherosclerotic controls, suggesting that this protein may pay a role in disease in vivo. In summary, the data presented here suggest an important regulatory role for trb-1 in vascular smooth muscle cell biology

Bioinformatics Analysis of the FREM1 Gene—Evolutionary Development of the IL-1R1 Co-Receptor, TILRR

The TLRs and IL-1 receptors have evolved to coordinate the innate immune response following pathogen invasion. Receptors and signalling intermediates of these systems are generally characterised by a high level of evolutionary conservation. The recently described IL-1R1 co-receptor TILRR is a transcriptional variant of the FREM1 gene. Here we investigate whether innate co-receptor differences between teleosts and mammals extend to the expression of the TILRR isoform of FREM1. Bioinformatic and phylogenetic approaches were used to analyse the genome sequences of FREM1 from eukaryotic organisms including 37 tetrapods and five teleost fish. The TILRR consensus peptide sequence was present in the FREM1 gene of the tetrapods, but not in fish orthologs of FREM1, and neither FREM1 nor TILRR were present in invertebrates. The TILRR gene appears to have arisen via incorporation of adjacent non-coding DNA with a contiguous exonic sequence after the teleost divergence. Comparing co-receptors in other systems, points to their origin during the same stages of evolution. Our results show that modern teleost fish do not possess the IL-1RI co-receptor TILRR, but that this is maintained in tetrapods as early as amphibians. Further, they are consistent with data showing that co-receptors are recent additions to these regulatory systems and suggest this may underlie differences in innate immune responses between mammals and fish

Enhanced macrophage tribbles-1 expression in murine experimental atherosclerosis.

Development of the atherosclerotic plaque involves a complex interplay between a number of cell types and an extensive inter-cellular communication via cell bound as well as soluble mediators. The family of tribbles proteins has recently been identified as novel controllers of pro-inflammatory signal transduction. The objective of this study was to address the expression pattern of all three tribbles proteins in atherosclerotic plaques from a mouse model of atherosclerosis. Each tribbles were expressed in vascular smooth muscle cells, endothelial cells as well as in resident macrophages of mouse atherosclerotic plaques. The role of IL-1 mediated inflammatory events in controlling tribbles expression was also addressed by inducing experimental atherosclerosis in ApoE-/-IL1R1-/- (double knockout) mice. Immunohistochemical analysis of these mice showed a selective decrease in the percentage of trb-1 expressing macrophages, compared to the ApoE-/- cohort (14.7% ± 1.55 vs. 26.3% ± 1.19). The biological significance of this finding was verified in vitro where overexpression of trb-1 in macrophages led to a significant attenuation (~70%) of IL-6 production as well as a suppressed IL-12 expression induced by a proinflammatory stimulus. In this in vitro setting, expression of truncated trb-1 mutants suggests that the kinase domain of this protein is sufficient to exert this inhibitory action

The Peculiar Type Ia Supernova 1999by: Spectroscopy at Early Epochs

We present medium resolution (lambda/Delta lambda = 2500) optical spectroscopy of SN 1999by in NGC 2841 made around its light maximum. The depth ratio of the two Si II features at 5800 AA and 6150 AA being R(SiII) approx. 0.63 at maximum indicates that this SN belongs to the peculiar, sub-luminous SNe Ia. Radial velocities inferred from the minimum of the 6150 AA trough reveal a steeper decline of the velocity curve than expected for ``normal'' SNe Ia, consistent with the behavior of published VRI light curves. A revised absolute magnitude of SN 1999by and distance to its host galaxy NGC 2841 is estimated based on the Multi-Color Light Curve Shape (MLCS) method, resulting in M_V(max)=-18.06+/- 0.1 mag and d = 17.1+/-1.2 Mpc, respectively. An approximative linear dependence of the luminosity parameter Delta on R(SiII) is presented.Comment: accepted for publication in Astron. Journal (2001 June

The IL-1RI co-receptor TILRR (FREM1 isoform 2) controls aberrant inflammatory responses and development of vascular disease

Summary Expression of the interleukin-1 receptor type I (IL-1RI) co-receptor Toll-like and interleukin-1 receptor regulator (TILRR) is significantly increased in blood monocytes following myocardial infarction and in the atherosclerotic plaque, whereas levels in healthy tissue are low. TILRR association with IL-1RI at these sites causes aberrant activation of inflammatory genes, which underlie progression of cardiovascular disease. The authors show that genetic deletion of TILRR or antibody blocking of TILRR function reduces development of atherosclerotic plaques. Lesions exhibit decreased levels of monocytes, with increases in collagen and smooth muscle cells, characteristic features of stable plaques. The results suggest that TILRR may constitute a rational target for site- and signal-specific inhibition of vascular disease

Cochlear implantation of a Hungarian deaf and blind patient with discharging ears suffering from Behçet's disease

A case is reported in which a Nucleus 22 channel intracochlear device was implanted a deaf/blind Hungarian adult with discharging ears suffering from Behçet's disease. Preconditioning surgery was employed three months prior to the implantation procedure to ensure a sterile, dry protected environment for the electrodes. One month after implantation, the patient exhibited excellent auditory discrimination capability at the time of the first switch on. We suggest that some deaf/blind individuals may serve as very good candidates for intracochlear implantatio

Retinal Blood Vessel Segmentation on Style-augmented Images

The average human lifespan increased dramatically in the second half of 20th century. It was mainly due to technological improvements, which were driven by the continuous war preparations, and while humans have got another 20 years to live, unfortunately there are some sad side effects added to the elderly life. Various diseases can attack the eye, our major organ responsible for receiving information, therefore many researches were devoted to examine these diseases, their early signs, and how could they be stopped. From the start of 21th century, methods aided by computer were more and more involved in these processes, up to the current trend of using Convolutional Neural Networks (CNNs). While supervised methods, CNNs do achieve accuracy which can be compared to a skilled ophtalmologist, they require a tremendous amount of labeled data which is sparse in medical fields because the amount of time and resources needed to create them. One natural solution is to augment the data present, that is, copying the distribution while adding a small variety, like coloring an image differently. That is, what our paper aims to explore, whether a texturing algorithm, the Neural Style Transfery can be used to make a data set richer, and therefore helping a classifier CNN to achieve better results. Received by the editors: 4 December 2020. 2010 Mathematics Subject Classification. 68U10, 68T01, 92B20. 1998 CR Categories and Descriptors. I.4.6 [I.2 Image Processing and Computer Vision]: Segmentation - Region, partitioning; I.5.1 [Pattern Recognition]: Models – Neural Nets

Western corn rootworm (Diabrotica virgifera virgifera LeConte) population dynamics

The western corn rootworm Diabrotica virgifera virgifera LeConte is a major insect pest of field maize, Zea mays L. Larvae can cause substantial injury by feeding on maize roots. Larval feeding may destroy individual roots or root nodes, and reduce plant growth, stability, and yield. Costs associated with managing corn rootworms in continuous maize are annually one of the largest expenditures for insect management in the United States Corn Belt. Even though D. virgifera virgifera has been studied intensively for over 50 years, there is renewed interest in the biology, ecology, and genetics of this species because of its ability to rapidly adapt to management tactics, and its aggressive invasive nature. This article provides a comprehensive review of D. virgifera virgifera population dynamics, specifically: diapause, larval and adult development, seasonality, spatial and temporal dynamics at local and landscape scales, invasiveness in North America and Europe, and non-trophic interactions with other arthropods. Gaps in current knowledge are identified and discussed especially within the context of challenges that scientists in North America and Europe are currently facing regarding pest dynamics and the need to develop appropriate management strategies for each geographic area

Identification of 34 Novel Proinflammatory Proteins in a Genome-Wide Macrophage Functional Screen

Signal transduction pathways activated by Toll-like Receptors and the IL-1 family of cytokines are fundamental to mounting an innate immune response and thus to clearing pathogens and promoting wound healing. Whilst mechanistic understanding of the regulation of innate signalling pathways has advanced considerably in recent years, there are still a number of critical controllers to be discovered. In order to characterise novel regulators of macrophage inflammation, we have carried out an extensive, cDNA-based forward genetic screen and identified 34 novel activators, based on their ability to induce the expression of cxcl2. Many are physiologically expressed in macrophages, although the majority of genes uncovered in our screen have not previously been linked to innate immunity. We show that expression of particular activators has profound but distinct impacts on LPS-induced inflammatory gene expression, including switch-type, amplifier and sensitiser behaviours. Furthermore, the novel genes identified here interact with the canonical inflammatory signalling network via specific mechanisms, as demonstrated by the use of dominant negative forms of IL1/TLR signalling mediators