The TID model for modulation of large scale electron density models

Various modern applications of empirical electron density models need realistic structures of the electron density distribution with smaller scales than the model background. Travelling Ionospheric Disturbances (TIDs) produce three dimensional and time dependent disturbances of the background ionization. We present a TID model suitable to «modulate» large scale electron density distributions by multiplication. A model TID takes into account the forward tilt of the disturbance wave front, a distinct vertical structure, a fan type horizontal radiation characteristic, geometric dilution and attenuation. More complicated radiation patterns can be constructed by means of superposition. The model TIDs originate from source regions which can be chosen arbitrarily. We show examples for TID modulations of the background model family developed at Trieste and Graz (NeQuick, COSTprof and NeUoG-plas)

An improved bottomside for the ionospheric electron density model NeQuick

The ionospheric electron density model NeQuick is a «profiler» which uses the peaks of the E-layer, the F1-layer and the F2-layer as anchor points. In the version prepared for and submitted to the International Telecommunication Union (ITU) the model uses the ITU-R (CCIR) maps for foF2 and M(3000)F2 and adapted maps similar to the ITU-R ones for foE and foF1. Since users found problematic behaviour of NeQuick under conditions of strong differences of foE and foF2 map structures, the profiling was adapted by changing the properties of the Epstein layers used for this purpose. The new formulation avoids both strange horizontal structures of the geographic distribution of electron density in fixed heights and unrealistic peculiarities of the height profile which occasionally occurred with the old version of the model. Since the Epstein layer approach allows for 8 parameters only (3 layer amplitudes and 5 semi-thicknesses) the adaptation was no minor task but needed careful planning of suitable strategies

Radio occultation techniques for probing the ionosphere

GPS radio occultation measurements establish the basis for a new remote sensing technique for vertical profile information on the electron density of the entire ionosphere from satellite orbit heights down to the bottomside. No other profiling technique such as vertical sounding or incoherent scatter, unifies vertical profiling through the entire ionosphere with global coverage. Inversion methods are described both for vertical profiling as well as for tree dimensional electron density reconstructions of the ionosphere. In three dimensional electron density reconstructions using signals from Global Navigation Satellite Systems (GNSS), the Ionospheric Radio Occultation (IRO) measurements provide vertical information which is complementary to the information obtained by ground based measurements. Assessment of achievable accuracy and spatial resolution are addressed by simulation studies. IRO measurements have been carried out onboard the German CHAMP satellite since 11 April 2001 on a routine basis. Assuming a spherically layered ionosphere, up to about 150 Electron Density Profiles (EDPs) per day are retrieved within a latency of 3 h. Validation results obtained by using independent data sources are reported. The validation with vertical sounding data in mid-latitudes indicates a small positive bias in the plasma frequency of up to about 0.5 MHz throughout the entire profile. Averages of the numerous EDPs show wellknown ionospheric phenomena such as the equatorial anomaly, the winter anomaly and the expansion of the profile with increasing solar energy input. It is concluded that CHAMP-IRO measurements have the potential to establish global data sets of vertical electron density profiles for developing and improving global ionospheric models and to provide operational space weather information

The clinical relevance of heme detoxification by the macrophage heme oxygenase system

Heme degradation by the heme oxygenase (HMOX) family of enzymes is critical for maintaining homeostasis and limiting heme-induced tissue damage. Macrophages express HMOX1 and 2 and are critical sites of heme degradation in healthy and diseased states. Here we review the functions of the macrophage heme oxygenase system and its clinical relevance in discrete groups of pathologies where heme has been demonstrated to play a driving role. HMOX1 function in macrophages is essential for limiting oxidative tissue damage in both acute and chronic hemolytic disorders. By degrading pro-inflammatory heme and releasing anti-inflammatory molecules such as carbon monoxide, HMOX1 fine-tunes the acute inflammatory response with consequences for disorders of hyperinflammation such as sepsis. We then discuss divergent beneficial and pathological roles for HMOX1 in disorders such as atherosclerosis and metabolic syndrome, where activation of the HMOX system sits at the crossroads of chronic low-grade inflammation and oxidative stress. Finally, we highlight the emerging role for HMOX1 in regulating macrophage cell death via the iron- and oxidation-dependent form of cell death, ferroptosis. In summary, the importance of heme clearance by macrophages is an active area of investigation with relevance for therapeutic intervention in a diverse array of human diseases

Unraveling the enigma of new-onset refractory status epilepticus: a systematic review of aetiologies

Background and purpose: New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active epilepsy or other pre-existing relevant neurological disorder, with a NORSE without a clear acute or active structural, toxic or metabolic cause. This study reviews the currently available evidence about the aetiology of patients presenting with NORSE and NORSE-related conditions. Methods: A systematic search was carried out for clinical trials, observational studies, case series and case reports including patients who presented with NORSE, febrile-infection-related epilepsy syndrome or the infantile hemiconvulsion-hemiplegia and epilepsy syndrome. Results: Four hundred and fifty records were initially identified, of which 197 were included in the review. The selected studies were retrospective case–control (n = 11), case series (n = 83) and case reports (n = 103) and overall described 1334 patients both of paediatric and adult age. Aetiology remains unexplained in about half of the cases, representing the so-called ‘cryptogenic NORSE’. Amongst adult patients without cryptogenic NORSE, the most often identified cause is autoimmune encephalitis, either non-paraneoplastic or paraneoplastic. Infections are the prevalent aetiology of paediatric non-cryptogenic NORSE. Genetic and congenital disorders can have a causative role in NORSE, and toxic, vascular and degenerative conditions have also been described. Conclusions: Far from being a unitary condition, NORSE is a heterogeneous and clinically challenging presentation. The development and dissemination of protocols and guidelines to standardize diagnostic work-up and guide therapeutic approaches should be implemented. Global cooperation and multicentre research represent priorities to improve the understanding of NORSE

An improved bottomside for the ionospheric electron density, model NeQuick

The ionospheric electron density model NeQuick is a «profiler» which uses the peaks of the E-layer, the F1-layer and the F2-layer as anchor points. In the version prepared for and submitted to the International Telecommunication Union (ITU) the model uses the ITU-R (CCIR) maps for foF2 and M(3000)F2 and adapted maps similar to the ITU-R ones for foE and foF1. Since users found problematic behaviour of NeQuick under conditions of strong differences of foE and foF2 map structures, the profiling was adapted by changing the properties of the Epstein layers used for this purpose. The new formulation avoids both strange horizontal structures of the geographic distribution of electron density in fixed heights and unrealistic peculiarities of the height profile which occasionally occurred with the old version of the model. Since the Epstein layer approach allows for 8 parameters only (3 layer amplitudes and 5 semi-thicknesses) the adaptation was no minor task but needed careful planning of suitable strategies

Evaluation of air oxidized PAPC: A multi laboratory study by LC-MS/MS

Oxidized LDL (oxLDL) has been shown to play a crucial role in the onset and development of cardiovascular disorders. The study of oxLDL, as an initiator of inflammatory cascades, led to the discovery of a variety of oxidized phospholipids (oxPLs) responsible for pro-inflammatory actions. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC) is frequently used by the scientific community as a representative oxPL mixture to study the biological effects of oxidized lipids, due to the high abundance of PAPC in human tissues and the biological activities of oxidized arachidonic acids derivatives. Most studies focusing on oxPAPC effects rely on in-house prepared mixtures of oxidized species obtained by exposing PAPC to air oxidation. Here, we described a multi-laboratory evaluation of the compounds in oxPAPC by LC-MS/MS, focusing on the identification and relative quantification of the lipid peroxidation products (LPPs) formed. PAPC was air-oxidized in four laboratories using the same protocol for 0, 48, and 72 h. It was possible to identify 55 different LPPs with unique elemental composition and characterize different structural isomeric species within these. The study showed good intra-sample reproducibility and similar qualitative patterns of oxidation, as the most abundant LPPs were essentially the same between the four laboratories. However, there were substantial differences in the extent of oxidation, i.e. the amount of LPPs relative to unmodified PAPC, at specific time points. This shows the importance of characterizing air-oxidized PAPC preparations before using them for testing biological effects of oxidized lipids, and may explain some variability of effects reported in the literature

S-layers at second glance? Altiarchaeal grappling hooks (hami) resemble archaeal S-layer proteins in structure and sequence

This is the final version of the article. Available from Frontiers Media via the DOI in this recordResearch on SM1-MSI was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft), grant no. MO 1977/3-1 given to CM-E. AJP was supported by the German National Academic Foundation (Studienstiftung des deutschen Volkes)

The collagen receptor discoidin domain receptor 1b enhances integrin β1-mediated cell migration by interacting with talin and promoting Rac1 activation.

Integrins and discoidin domain receptors (DDRs) 1 and 2 promote cell adhesion and migration on both fibrillar and non fibrillar collagens. Collagen I contains DDR and integrin selective binding motifs; however, the relative contribution of these two receptors in regulating cell migration is unclear. DDR1 has five isoforms (DDR1a-e), with most cells expressing the DDR1a and DDR1b isoforms. We show that human embryonic kidney 293 cells expressing DDR1b migrate more than DDR1a expressing cells on DDR selective substrata as well as on collagen I in vitro. In addition, DDR1b expressing cells show increased lung colonization after tail vein injection in nude mice. DDR1a and DDR1b differ from each other by an extra 37 amino acids in the DDR1b cytoplasmic domain. Interestingly, these 37 amino acids contain an NPxY motif which is a central control module within the cytoplasmic domain of β integrins and acts by binding scaffold proteins, including talin. Using purified recombinant DDR1 cytoplasmic tail proteins, we show that DDR1b directly binds talin with higher affinity than DDR1a. In cells, DDR1b, but not DDR1a, colocalizes with talin and integrin β1 to focal adhesions and enhances integrin β1-mediated cell migration. Moreover, we show that DDR1b promotes cell migration by enhancing Rac1 activation. Mechanistically DDR1b interacts with the GTPase-activating protein (GAP) Breakpoint cluster region protein (BCR) thus reducing its GAP activity and enhancing Rac activation. Our study identifies DDR1b as a major driver of cell migration and talin and BCR as key players in the interplay between integrins and DDR1b in regulating cell migration

Impaired dermal wound healing in discoidin domain receptor 2-deficient mice associated with defective extracellular matrix remodeling

Background The wounding response relies on tightly regulated crosstalk between recruited fibroblasts and the collagenous extracellular matrix (ECM). Discoidin domain receptor 2 (DDR2) is a tyrosine kinase receptor for fibrillar collagen expressed during pathologic scarring, for example wound healing, arthritis and cancer. We have previously shown that DDR2 phosphorylation drives key wounding responses in skin fibroblasts including proliferation, chemotactic migration and secretion of both metalloproteinases and fibrillar collagen. In this study we compared healing of cutaneous wounds in DDR2+/+ and DDR2-/- mice and analyzed specific fibroblast responses. Results Cutaneous wound healing was significantly delayed in DDR2-/- mice compared with DDR2+/+ animals. Reduced α-smooth muscle actin (αSMA) expression and matrix metalloproteinase 2 (MMP2) activity in the DDR2-/- wound extracts indicated defective recruitment of skin fibroblasts. DDR2-/- wounds showed decreased tensile strength during healing, which correlated with a significant reduction in collagen content and defective collagen crosslinking. Non-wounded skin in DDR2-/- mice expressed less mRNA of the crosslinking enzymes lysyl oxidase (LOX), lysyl hydroxylase1 (LH1) and matricellular 'secreted protein, acidic and rich in cysteine' (SPARC; also known as osteonectin). Skin fibroblasts isolated from DDR2-/- mice displayed altered mRNA expression of a cluster of collagens, proteoglycans, integrins and MMPs that have been previously correlated with DDR2 expression, and reduced LOX, LH1 and SPARC mRNA levels and proteins. Stable reconstitution of wild-type DDR2 by retroviral infection restored LOX, LH1 and SPARC mRNA and protein levels in DDR2-/- fibroblasts. Contraction of collagen gels was reduced in DDR2-/- fibroblasts, accompanied by significantly reduced phosphorylated SrcY418. Inhibition of either LOX activity by β-aminoproprionitrile or MMP activity by N-[(2R)-2-(hydroxamido carbonylmethyl)-4-methylpentanoyl]-l-tryptophan methylamide (GM6001) reduced collagen gel contraction by skin fibroblasts after DDR2 induction with soluble collagen type I. Conclusions DDR2 contributes to skin fibroblast responses during tissue injury. Defective synthesis of collagen type I, crosslinking molecules and MMP2 predispose DDR2-/- mice to defective dermal wounding