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The assessment of global warming and its far-reaching influences on our planet necessitates reliable and accurate climate models. For this purpose, past atmospheric conditions like aerosol composition must be studied to understand their influence on the Earth’s climate. Ice cores are valuable climate archives that preserve organic compounds from atmospheric aerosols, which can be utilized as marker species for their respective emission sources.Secondary organic aerosols (SOAs) are formed in the atmosphere by the oxidation of volatile organic compounds (VOCs), which can be either of anthropogenic or biogenic origin. The most common precursors of SOAs are monoterpenes, which are naturally emitted by vegetation in large amounts. Furthermore, organic compounds formed during biomass burning events contribute to the aerosol budget and allow the reconstruction of paleo-fire activity. Of great interest as a marker species is the anhydrosugar levoglucosan, which is formed during the combustion of cellulose. In addition to its combustion products, intact polymeric lignin, digested via alkaline oxidative degradation, can provide information about the type of vegetation which it originated from. A large variety of these markers were analyzed in an ice core extracted from the Belukha glacier located in the Altai region of Southern Siberia covering a time span of three centuries. A sample preparation method including multiple solid phase extractions and UHPLC-HRMS analysis was employed.Chiral compounds have the same molecular formula and atom connectivity but act like mirror images of each other. In most environmental studies, no distinction is made between these so-called enantiomers. However, chirality can affect chemical and physical properties and thus influence particle formation reactions in the atmosphere. The enantiomeric ratio of a chiral compound can also further elucidate possible emission sources. Here we present the first chiral analysis of monoterpene oxidation products in ice cores and thus on a long-term scale. For this purpose, a multiple heartcut two-dimensional liquid chromatography method (mLC-LC) was developed that allows the simultaneous determination of the enantiomeric ratios of the monoterpene oxidation products cis-pinic acid and cis-pinonic acid in complex ice core samples. This novel method was successfully applied to Belukha ice core samples.

In the European Union a disease is classified as rare if it affects no more than 5 out of 10,000 people. Currently, there are more than 6000 rare diseases, consisting of a large and heterogeneous number of different diseases that are complex in their symptomatology, multidimensional and therefore difficult to classify in everyday medical practice. This complicates the diagnosis and treatment as well as finding a suitable contact person, as there are only a few experts for each individual rare disease. The medical care atlas for rare diseases www.se-atlas.de enables the search for care facilities and patient organizations for specific rare diseases by disease name and presents the search results geographically. It also provides an overview of all German centers for rare diseases, which are a contact point for patients with an unclear diagnosis. The se-atlas serves as a compass through the heterogeneous amount of information on care facilities for rare diseases and provides low-threshold information for a broad user group, from affected persons to members of the medical care team.Eine Erkrankung zählt in der Europäischen Union zu den Seltenen Erkrankungen (SE), wenn diese nicht mehr als 5 von 10.000 Menschen betrifft. Derzeit existiert mit mehr als 6000 SE eine sowohl große als auch heterogene Menge an unterschiedlichen Krankheitsbilder, die in ihrer Symptomatik komplex, vielschichtig und damit im medizinischen Alltag schwierig einzuordnen sind. Dies erschwert Diagnosefindung und Behandlung sowie das Auffinden eines passenden Ansprechpartners, da es nur wenige Experten für jede einzelne SE gibt. Der medizinische Versorgungsatlas für Seltene Erkrankungen www.se-atlas.de ermöglicht anhand von Erkrankungsnamen die Suche nach Versorgungseinrichtungen und Selbsthilfeorganisationen zu bestimmten SE und stellt die Suchergebnisse geografisch dar. Ebenso gibt er einen Überblick über alle deutschen Zentren für SE, die eine Anlaufstelle für betroffene Personen mit unklarer Diagnose darstellen. Der se-atlas dient als Kompass durch die heterogene Menge an Informationen über Versorgungseinrichtungen für SE und stellt niederschwellig Informationen für eine breite Nutzergruppe von Betroffenen bis hin zu Mitgliedern des medizinischen Versorgungsteams bereit.

TNF blockade is a successful treatment for human autoimmune disorders like rheumatoid arthritis and inflammatory bowel disease yet increases susceptibility to tuberculosis and other infections. The C-type lectin receptors (CLR) MINCLE, MCL, and DECTIN-2 are expressed on myeloid cells and sense mycobacterial cell wall glycolipids. In this study, we show that TNF is sufficient to upregulate MINCLE, MCL, and DECTIN-2 in macrophages. TNF signaling through TNFR1 p55 was required for upregulation of these CLR and for cytokine secretion in macrophages stimulated with the MINCLE ligand trehalose-6,6-dibehenate or infected with Mycobacterium bovis bacillus Calmette–Guérin. The Th17 response to immunization with the MINCLE-dependent adjuvant trehalose-6,6-dibehenate was specifically abrogated in TNF-deficient mice and strongly attenuated by TNF blockade with etanercept. Together, interference with production or signaling of TNF antagonized the expression of DECTIN-2 family CLR, thwarting vaccine responses and possibly increasing infection risk.

Ice cores are valuable climate archives preserving organic compounds from atmospheric aerosols over long time ranges. Different approaches of dating are available like annual layer counting, radioactive decay and stratigraphic markers like tephra from volcanic eruption. In combination, they enable accurate dating back to 800,000 years. Secondary organic aerosols (SOA) are formed in the atmosphere by condensation of oxidized highly volatile organic compounds and their chemical profile is highly complex due to the variety of emission sources and reactions in the atmosphere.Well-known SOA markers include pinic acid, pinonic acid or terebic acid from monoterpene oxidation. Another class of important atmospheric markers are biomass burning products. During combustion of cellulose levoglucosan, an anhydrosugar is formed while the combustion of lignin results in the formation of phenolic compounds like vanillic acid, cinnamic acid, or p-hydroxybenzoic acid. While the lignin burning products provide important information on paleo-fire history, intact polymeric lignin offers a deeper insight into the type and abundance of vegetation. By alkaline oxidation, the polymeric lignin is degraded into the lignin oxidation products (LOP) and the ratios of these products are related to wooden and non-wooden, as well as angiosperm and gymnosperm vegetation.In this work, an analytical approach is presented covering a variety of SOA markers, biomass burning markers, and polymeric lignin, using UHPLC-HRMS and an elaborate sample preparation procedure. The method was applied to samples from Colle Gnifetti in the Swiss-Italian Alps, a part of Grenzgletscher, covering the time between 1920 and 1994. We present first data on polymeric lignin in ice core samples and an examination of correlations with known organic proxies to emphasize the relevance of lignin not only in climate archives like speleothems and sediments but also in ice core samples.

Abstract Cyclodipeptide oxidases (CDOs) perform dehydrogenations on diketopiperazines and play an important role in the cyclodipeptide diversification. In this study, we investigated the two known CDOs AlbA/B and Ndas_1146/7 and one new member, CDO-Np. LC-MS monitoring of 32 cyclodipeptide biotransformations in E. coli revealed good consumption of cyclodipeptides containing aromatic amino acids. Cyclodipeptides consisting solely of aliphatic amino acids were poor substrates. In vitro assays of 34 substrates with crude enzyme extracts and product identification proved that the CDO-Np-containing extract catalyzes the formation of two C–C double bonds in many cases. The extracts containing the two other enzymes had lower activities and catalyzed mainly didehydrogenations. For didehydrogenation, the phenylalanyl or tyrosyl site was usually preferred. No or very low acceptance of benzodiazepinediones and a 2,6-diketopiperazine proved the importance of the 2,5-diketopiperazine ring. N-Methylation at the diketopiperazine ring or prenylation of the tryptophan-containing cyclodipeptides influences the enzyme activity and product spectrum. Key points • Comparison of catalytic activities of three enzymes; Diverse cyclodipeptides and derivatives as substrates; Determination of double bond formation using2H-labeled substrates; Product identification also by interpretation of MS2fragmentation pattern.

Experimental cutaneous leishmaniasis of mice is a valuable model to study the immune response to the protozoan pathogen Leishmania and to define mechanisms of parasite control and resolution of inflammation as well as of parasite evasion and chronicity of disease. In addition, over many years Leishmania-infected mice have been successfully used to analyze the function of newly discovered immune cell types, transcription factors, cytokines, and effector mechanisms in vivo. In this chapter we present detailed protocols for the culture, propagation, and inoculation of Leishmania promastigotes, the monitoring of the course of cutaneous infection, the determination of the tissue parasite burden and for the phenotyping of the ensuing immune response. The focus lies on the L. major mouse model, but an overview on other established models of murine cutaneous leishmaniasis is also provided.

Experimental cutaneous leishmaniasis of mice is a valuable model to study the immune response to the protozoan pathogen Leishmania and to define mechanisms of parasite control and resolution of inflammation as well as of parasite evasion and chronicity of disease. In addition, over many years Leishmania-infected mice have been successfully used to analyze the function of newly discovered immune cell types, transcription factors, cytokines, and effector mechanisms in vivo. In this chapter we present detailed protocols for the culture, propagation, and inoculation of Leishmania promastigotes, the monitoring of the course of cutaneous infection, the determination of the tissue parasite burden and for the phenotyping of the ensuing immune response. The focus lies on the L. major mouse model, but an overview on other established models of murine cutaneous leishmaniasis is also provided.

A Gram-negative bacterium, designated E130T, was isolated from rhizospheric soil of Plantago winteri Wirtg. from a natural salt meadow as part of an investigation on rhizospheric bacteria from salt-resistant plant species and evaluation of their plant growth-promoting abilities. Cells were rods, non-motile, aerobic, and oxidase and catalase positive, grew in a temperature range of between 4 and 37 °C, and in the presence of 0.5–5 % NaCl (w/v). Based on 16S rRNA gene sequence analysis, strain E130T is affiliated within the genus Ancylobacter , sharing the highest similarity with Ancylobacter rudongensis DSM 17131T (97.6 %), Ancylobacter defluvii CCUG 63806T (97.5 %) and Ancylobacter dichloromethanicus DSM 21507T (97.4 %). The DNA G+C content of strain E130T was 65.1 mol%. Its respiratory quinones were Q-9 and Q-10 and its major polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and unidentified phospholipid. Major fatty acids of the strains E130T were C12 : 0, C16 : 0, C18 : 1 ω7c and C19 : 0cyclo ω8c. The DNA–DNA relatedness of E130T to A. rudongensis DSM 17131T , A. defluvii CCUG 63806T and A. dichloromethanicus DSM 21507T was 29.2, 21.2 and 32.2 % respectively. On the basis of our polyphasic taxonomic study the new isolate represents a novel species, for which the name Ancylobacter pratisalsi sp. nov. is proposed. The type strain is E130T (LMG 29367T=DSM 102029T).

Hemophagocytic lymphopcytosis (HLH) is a life-threatening condition. It can occur either as primary form with genetic defects or secondary to other conditions, such as hematological or autoimmune diseases. Certain triggering factors can predispose individuals to the development of HLH. We report the case of a 25-year-old male patient who was diagnosed with HLH in the context of adult-onset Still's disease (AOSD) during a primary infection with Epstein-Barr virus (EBV). During therapy with anakinra and dexamethasone, he was still symptomatic with high-spiking fevers, arthralgia, and sore throat. His laboratory values showed high levels of ferritin and C-reactive protein. His condition improved after the addition of rituximab and cyclosporine to his immunosuppressive regimen with prednisolone and anakinra. This combination therapy led to a sustained clinical and serological remission of his condition. While rituximab has been used successfully for HLH in the context of EBV-associated lymphoma, its use in autoimmune diseases is uncommon. We hypothesize that the development of HLH was triggered by a primary EBV infection and that rituximab led to elimination of EBV-infected B-cells, while cyclosporine ameliorated the cytokine excess. We therefore propose that this combination immunosuppressive therapy might be successfully used in HLH occurring in the context of autoimmune diseases.

Good-quality single crystals of the title compound, indigo B [systematic name: 2-(3-oxoindolin-2-ylidene)indolin-3-one], C16H10N2O2, have been prepared with high selectivity by a sublimation process. The previous structure of indigo B [Süsse & Wolf (1980). Naturwissenschaften, 67, 453], which showed that the complete molecule is generated by crystallographic inversion symmetry has been confirmed, but the present study reports more realistic geometrical parameters and modern standards of precision (e.g. σ for C—C bonds = 0.002–0.003 Å). Each molecule features two intramolecular N—H...O hydrogen bonds. In the crystal, molecules are linked by strong face-to-face π–π stacking interactions involving both the six- and five-membered rings [centroid–centroid separations = 3.6290 (14) and 3.6506 (14) Å] and intermolecular N—H...O hydrogen bonds.