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Background Atopic dermatitis (AD) is driven by the interplay between a dysfunctional epidermal barrier and a skewed cutaneous immune dysregulation. As part of the complex skin barrier dysfunction, abnormalities in lipid organization and microbiome composition have been described. We set out to systematically investigate the composition of the stratum corneum lipidome, skin microbiome and skin physiology parameters at three different body sites in patients with AD and healthy volunteers. Methods We analysed tape strips from different body areas obtained from 10 adults with AD and 10 healthy volunteers matched for FLG mutation status for 361 skin lipid species using the Metabolon mass spectrometry platform. 16S rRNA data were available from all probands. Results Our study showed that the lipid composition differs significantly between body sites and between AD patients and healthy individuals. Ceramide species NS was significantly higher in AD patients compared to healthy volunteers and was also higher in AD patients with a FLG mutation compared to AD patients without a FLG mutation. The correlation analysis of skin lipid alterations with the microbiome showed that Staphylococcus colonization in AD is positively correlated with ceramide subspecies AS, ADS, NS and NDS. Conclusion This is the first study to reveal site-specific lipid alterations and correlations with the skin microbiome in AD

Simulation of the furnace of the boiler P-49 in the package of applied programs fire 3D

The combustion of solid low-grade fuel in LTV-boiler furnaces is a pressing research questions currently. The aim of this work is the creation of a computational grid model LTV-furnace to calculate the package of applied programs FIRE 3D. The study created a model LTV-furnace. The model tested on brown coal from the Nazarovo Deposit. The resulting distribution of temperatures and velocities has proved the performance of the model

The Rac1 Inhibitor NSC23766 Exerts Anti-Influenza Virus Properties by Affecting the Viral Polymerase

The frequent emergence of new influenza viruses in the human population underlines the urgent need for antiviral therapeutics in addition to the preventative vaccination against the seasonal flu. To circumvent the development of resistance, recent antiviral approaches target cellular proteins needed by the virus for efficient replication. We investigated the contribution of the small GTPase Rac1 to the replication of influenza viruses. Inhibition of Rac1 by NSC23766 resulted in impaired replication of a wide variety of influenza viruses, including a human virus strain of the pandemic from 2009 as well as highly pathogenic avian virus strains. Furthermore, we identified a crucial role of Rac1 for the activity of the viral polymerase complex. The antiviral potential of NSC23766 was confirmed in mouse experiments, identifying Rac1 as a new cellular target for therapeutic treatment of influenza virus infections

Influence of wavelength and accumulated fluence at picosecond laser-induced surface roughening of copper on secondary electron yield

Ultrashort-pulse laser processing of copper is performed in air to reduce the secondary electron yield (SEY). By UV (355 nm), green (532 nm), and IR (1064 nm) laser-light induced surface modification, this study investigates the influence of the most relevant experimental parameters, such as laser power, scanning speed, and scanning line distance (represented as accumulated fluence) on the ablation depth, surface oxidation, topography, and ultimately on the SEY. Increasing the accumulated laser fluence results in a gradual change from a Cu 2 O to a CuO-dominated surface with deeper micrometer trenches, higher density of redeposited surface particles from the plasma phase, and a reduced SEY. While the surface modifications are less pronounced for IR radiation at low accumulated fluence (,1000 J/cm2 ), analogous results are obtained for all wavelengths when reaching the nonlinear absorption regime, for which the SEY maximum converges to 0.7. Furthermore, independent of the extent of the structural transformations, an electron-induced surface conditioning at 250 eV allows a reduction of the SEY maximum below unity at doses of 5×10 -4 C/mm2 . Consequently, optimization of processing parameters for application in particle accelerators can be obtained for a sufficiently low SEY at controlled ablation depth and surface particle density, which are factors that limit the surface impedance and the applicability of the material processing for ultrahigh vacuum systems. The relations between pro- cessing parameters and surface features will provide guidance in treating the surface of vacuum components, especially beam screens of selected magnets of the Large Hadron Collider or of future colliders

Signal Transduction in the Footsteps of Goethe and Schiller

The historical town of Weimar in Thuringia, the "green heart of Germany" was the sphere of Goethe and Schiller, the two most famous representatives of German literature's classic era. Not yet entirely as influential as those two cultural icons, the Signal Transduction Society (STS) has nevertheless in the last decade established within the walls of Weimar an annual interdisciplinary Meeting on "Signal Transduction – Receptors, Mediators and Genes", which is well recognized as a most attractive opportunity to exchange results and ideas in the field

A Plant Extract of Ribes nigrum folium Possesses Anti-Influenza Virus Activity In Vitro and In Vivo by Preventing Virus Entry to Host Cells

Infections with influenza A viruses (IAV) are still amongst the major causes of highly contagious severe respiratory diseases not only bearing a devastating effect to human health, but also significantly impact the economy. Besides vaccination that represents the best option to protect from IAV infections, only two classes of anti-influenza drugs, inhibitors of the M2 ion channel and the neuraminidase, often causing resistant IAV variants have been approved. That is why the need for effective and amply available antivirals against IAV is of high priority. Here we introduce LADANIA067 from the leaves of the wild black currant (Ribes nigrum folium) as a potent compound against IAV infections in vitro and in vivo. LADANIA067 treatment resulted in a reduction of progeny virus titers in cell cultures infected with prototype avian and human influenza virus strains of different subtypes. At the effective dose of 100 µg/ml the extract did not exhibit apparent harming effects on cell viability, metabolism or proliferation. Further, viruses showed no tendency to develop resistance to LADANIA067 when compared to amantadine that resulted in the generation of resistant variants after only a few passages. On a molecular basis the protective effect of LADANIA067 appears to be mainly due to interference with virus internalisation. In the mouse infection model LADANIA067 treatment reduces progeny virus titers in the lung upon intranasal application. In conclusion, an extract from the leaves of the wild black currant might be a promising source for the development of new antiviral compounds to fight IAV infections

Sickle cell trait (HbAS) and stunting in children below two years of age in an area of high malaria transmission

<p>Abstract</p> <p>Background</p> <p>While the protective effects of sickle cell trait (HbAS) against severe malaria and the resulting survival advantage are well known, the impact on the physical development in young children remains unclear. This study was aimed to investigate the relationship between HbS carriage and stunting in children below two years of age in a cohort from the Ashanti Region, Ghana.</p> <p>Methods</p> <p>1,070 children were recruited at three months of age and followed-up for 21 months with anthropometric measurements performed every three months. Incidence rate ratios with 95% confidence intervals were calculated by Poisson regression to estimate the association of β-globin genotypes with the number of malaria episodes. Odds ratios (OR) were calculated for the association between the occurrence of β-globin genotypes and/or malaria episodes and stunting. The age-dependent between-group and within-group effects for the β-globin genotypes were assessed by population-averaged models estimated by generalized estimation equation with autoregressive correlation structure.</p> <p>Results</p> <p>Analyses showed a significantly lower age-dependent risk of stunting (OR 0.56; 95% CI 0.33–0.96) in carriers of the HbAS genotype (n = 102) in comparison to those with HbAA (n = 692). This effect was restricted to children who experienced malaria episodes during the observation period suggesting that the beneficial effect of the β-globin HbS variant on the incidence of stunting is closely linked to its protection from mild malaria episodes.</p> <p>Conclusion</p> <p>The lower risk of chronic malnutrition in early childhood, mediated by protection against mild malaria episodes, may contribute to the survival advantage of HbAS carriers in areas of high malaria transmission.</p

Risk of Human Immunodeficiency Virus Type 1-Related Neurologic Disease in a Cohort of Intravenous Drug Users

Background: Although the proportion of cases of acquired immunodeficiency syndrome related to intravenous drug use has increased dramatically over the past decade, there has been no longitudinal examination of primary neurologic disease in this group. Objective: To study the development of neurologic disease in human immunodeficiency virus (HIV)—negative and HIV-positive men and women who were intravenous drug users over a 3.5-year period. Design: Prospective observational cohort study. Setting: Subjects were recruited from an infectious disease clinic at a New York City Hospital or from a methadone maintenance program. Participants: Ninety-nine HIV-negative (62 men and 37 women) and 124 HIV-positive (85 men and 39 women) intravenous drug users volunteered. Main Outcome Measure: The development of clinically significant manifestations in six neurologic domains. Results: With multivariate adjustment for current and past substance abuse, age, education, and head injury, we examined the odds of developing HIV-related neurologic disease. Extrapyramidal signs and reduced motor ability became increasingly apparent over time in HIV-infected men as their CD4 cell count declined and as the subjects developed the acquired immunodeficiency syndrome. Fewer neurologic signs were seen in the women. Conclusions: The impact of HIV infection among intravenous drug users parallels that in homosexual men and is independent of alcohol and other drug use

Neurologic and Neuropsychological Manifestations of Human Immunodeficiency Virus Infection in Intravenous Drug Users without Acquired Immunodeficiency Syndrome. Relationship to Head Injury

We examined 99 human immunodeficiency virus (HIV)—negative and 122 HIV-positive intravenous drug users (IVDUs) without acquired immunodeficiency syndrome (AIDS) to determine whether HIV-positive IVDUs had more neurologic and neuropsychological impairment than their HIV-negative counterparts. Controlling for age, education, drug use, history of head injury, and interactions between head injury and HIV status and drug use, HIV-positive subjects had more extrapyramidal signs and frontal release signs. These findings persisted when asymptomatic HIV-positive subjects without systemic signs of infection and HIV-negative subjects were compared. Neurologic findings were more severe in those with more systemic illness. Among those reporting a history of head injury with loss of consciousness, neuropsychological performance was significantly worse in the HIV-positive subjects, and this increased with severity of illness. This was not true in the group without head injury, suggesting an interaction between history of head injury and the seropositive state. No relationship was noted between head injury and either drug use or HIV state. Therefore, subtle neurologic and neuropsychological abnormalities may precede clinical evidence of AIDS in IVDUs and may be more evident in those with head injury