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Asthma and allergy incidence continue to increase globally. We have made significant strides in treating disease, but it is becoming more apparent that we need to advance our knowledge into the origins of asthmatic disease. Much recent work has indicated that microbiome composition influences immune regulation and that multiple health care factors have driven a loss in microbiome diversity in modern human populations. Evidence is growing of microbiota-driven influences on immune development, asthma susceptibility, and asthma pathogenesis. The focus of this review is to highlight the strides the field has made in characterizing the constituents of the human gastrointestinal microbiota, such as Helicobacter pylori, other members of the neonatal intestinal microbiota, and microbial peptides and metabolites that influence host immunity and immune response to allergens. As we delve further into this field of research, the goal will be to find actionable and clinical interventions to identify at-risk populations earlier to prevent disease onset. Manipulation of the host microbial community during infancy might be an especially promising approach.

Summary Despite overall success, T cell checkpoint inhibitors for cancer treatment are still only efficient in a minority of patients. Recently, intestinal microbiota was found to critically modulate anti-cancer immunity and therapy response. Here, we identify Clostridiales members of the gut microbiota associated with a lower tumor burden in mouse models of colorectal cancer (CRC). Interestingly, these commensal species are also significantly reduced in CRC patients compared with healthy controls. Oral application of a mix of four Clostridiales strains (CC4) in mice prevented and even successfully treated CRC as stand-alone therapy. This effect depended on intratumoral infiltration and activation of CD8+ T cells. Single application of Roseburia intestinalis or Anaerostipes caccae was even more effective than CC4. In a direct comparison, the CC4 mix supplementation outperformed anti-PD-1 therapy in mouse models of CRC and melanoma. Our findings provide a strong preclinical foundation for exploring gut bacteria as novel stand-alone therapy against solid tumors.

Jacks et al. (2011) offer an alternative to price gaps to quantify trade costs. Implementing a method which consists in deducing international trade costs from trade flows, they argue that the reduction in trade costs was the main driving force of trade growth during the first globalization (1870-1913), whereas economic expansion was the main driving force during the second globalization (1950-2000). We argue that this important result is driven by the use of an ad hoc aggregation method. What Jacks et al. (2011) capture is the difference in the relative starting trade of dyads experiencing faster trade growth in the first and second globalization. More generally, we cast doubts on the possibility to reach conclusions of such nature with a method that infers trade costs from trade flows, and then uses these costs to explain trade flows. We argue that it can only rephrase the information already contained in openness ratios.

Carbohydrate scaffolds, functionalised according to an AB4-type, were prepared on the basis of α-D-mannopyranosides with various ethyl aglycone moieties, functionalised with 'A'. Four functional groups 'B' were installed at positions 2, 3, 4, and 6 of the sugar ring. In particular, we were interested in preparing N3(NH2)4-functionalised mannosides as multifunctional branching units for further orthogonal derivatisation or immobilisation on surfaces. A detailed synthetic study was performed which revealed that an azido function 'A' had to be installed at an advanced stage of the synthesis for successful preparation of the desired AB4-type carbohydrate scaffolds. The most successful synthetic sequence involved tetra-cyanoethylation of a 2-benzyloxyethyl mannopyranoside and subsequent reduction with in situ Boc protection to achieve (NHBoc)4 functionalisation. Finally, the benzyloxyethyl aglycon was converted into the corresponding azidoethyl moiety to gain access to the desired N3(NHBoc)4-functionalised carbohydrate scaffold. Its utilisation was exemplified by straightforward synthesis of a photosensitive glycoconjugate and a tetravalent glycocluster. Such compounds may be immobilised on functional surfaces to serve as tools in cell adhesion studies.

A soil microcosm experiment was performed to assess (1) the C- and N- turnover of residues from biogas plants in soils in the presence of three earthworm species ( Lumbricus terrestris , Aporrectodea longa and Aporrectodea caliginosa ) and (2) the resulting changes in soil chemical and microbiological properties when using these residues as fertilizer in comparison to conventional slurry. Earthworms were exposed in soils, fertilized with an equivalent amount of 120 kg of NH 4 -N ha −1 from: (1) conventional cattle slurry and (2) a fermented residue derived from cattle slurry, grass (silage) and maize. Additional treatments without slurry and earthworms were used as controls. There was considerable evidence that soils fertilized by fermented slurry comprised fewer amounts of readily available nutrients for microbial C and N turnover. We observed significant stimulation of microbial biomass, basal respiration and nitrification in treatments with conventional slurry, especially in the presence of earthworms. However, the stimulation of microbial activity by manure and earthworms were significantly lower in treatments with fermented slurry. Moreover, the results showed clear interactions between different earthworm species and manures. While the biomass of the anecic species ( L. terrestris and A. longa ) increased in both slurry treatments, the biomass of A. caliginosa (endogeic) decreased, with a significantly stronger biomass decline in treatments with fermented slurry. The metabolic quotients revealed microbial stress metabolism in fermented slurry treatments, predominantly in treatments with A. caliginosa . We conclude that particularly A. caliginosa and soil microorganisms competed for labile C sources in treatments with fermented slurry. An application of these residues as fertilizer might result in a reduction of microbial activity in agricultural soils and in a decline of endogeic earthworms.

Analysis of shape variability of anatomical structures is a widespread problem on one hand and an essential fundament for the analysis of biological processes and the diagnosis of a large spectrum of pathologies on the other hand. Many diseases affecting the middle ear result from morphological alterations and provoke morphological changes of the middle ear cavity. Therefore, it was our goal to analyze shape and shape variations of a population of this anatomical structure.By segmenting and modeling 10 middle ear cavities using a medial-based representation, which provides inter-individual correspondence, a common shape model of the tympanic cavity has been generated. The results show that medial-based representation is suitable to generate a common shape model of the tympanic cavity and to provide a facility to analyze the complex shape of the anatomical structure and the physiological variations.

Near-infrared spectroscopy (NIRS) is a noninvasive method that allows the assessment of activation-induced cortical oxygenation changes in humans. It has been demonstrated that an increase in oxygenated and a decrease in deoxygenated haemoglobin can be expected over an area activated by functional stimulation. Likewise, an inverse oxygenation pattern has been shown to be associated with cortical deactivation. The aim of the current study was to determine the oxygenation changes that occur during absence seizures. We performed ictal NIRS simultaneously with video-EEG telemetry in three adult patients with typical absence seizures. NIRS probes were placed over the frontal cortex below the F1/F2 leads. During all absence seizures studied, pronounced changes in cerebral Hb-oxygenation were noted and there were no changes in the interval. We observed a reproducible decrease in [oxy-Hb] and an increase in [deoxy-Hb] during absence seizures indicating a reduction of cortical activity. Oxygenation changes started several seconds after the EEG-defined absence onset and outlasted the clinically defined event by 20-30 s.

The accumulation and storage of trace metals in coastal sediments is an environmental concern. It is, therefore, important to understand better how these metals are bound or released under different redox conditions. This study of Fe and trace metal fixation under continuously anoxic conditions in the bottom sediments and the lower water column of the Nordasvannet fjord in western Norway contributes further to such understanding. It allows investigation of both an end member redox state and one important mechanism of Fe and trace metal accumulation in sediments, the pyritization of Fe and trace metals. Pyrite formation occurs both in the water column and in the sediments of the Nordasvannet fjord and favours the fixing of Fe and trace metals in the bottom sediments of the fjord. Thus, these sediments act as a continuous sink for Fe and trace metals. The DOP, and the degrees of trace metal pyritization for Mo, Ni and Cr correlate with organic matter content. While it is generally thought that Fe is the factor limiting pyrite formation in anoxic environments, this study found that degrees of pyritization of Fe (DOP) are clearly below 100%, and the availability of metabolizable organic matter is limiting pyrite formation. This is an important finding, because it indicates that increased supply of organic and mineral matter by higher runoff from land would further enhance the fixation of these metals in the fjord sediments, as would higher organic matter availability from increased productivity due to higher nutrient supply. The metals stored in the bottom sediments could be released into the biogeochemical cycle if redox conditions were to change from anoxic to suboxic or oxic. The fjord would then become a source rather than a sink for these metals.

Organic C burial rates and C–S relationships were investigated in the Holocene sediment sequences of 3 shallow polymictic coastal lagoons in the southern Baltic Sea to better understand the biogeochemical cycling of C and S in these environmental systems. The results show that these lagoons may have a considerable influence on the environmental status of the southern Baltic Sea area in having the potential to act as a temporary sink or source for heavy metals. High organic C accumulation rates (Corg-AR) can be observed in the sediments due to a high organic matter supply from land and a high productivity of the water bodies as a result of eutrophication. However, organic C burial does not increase as a result of increasing sediment accumulation rates (SAR). Even when high sedimentation rates do occur, there appears to be a thorough recycling and resuspension of the sediment enhancing the biological decay of organic matter before burial or the removal of organic matter from the system by transport. That is why high SAR in the coastal lagoons do not enhance pyrite formation, and thereby permanent fixing of heavy metals in the sediments, to the extent that could be expected from their magnitude. Initially there is a high potential for a temporary binding of heavy metals, but the latter are likely to be subject to mobilization and redistribution within the sediments and the water column. The patterns of burial of organic and mineral matter are different from those observed in the present-day Baltic Proper, implying possible important links in deposition between the central and coastal areas of the Baltic Sea and implications for C cycling in the ecosystem of the Baltic Sea.

This paper describes a fast and simple pressurized liquid extraction method for the determination of polychlorinated biphenyls (PCBs) in feedingstuffs and food matrices. The method is based on a simultaneous extraction/clean-up step requiring a minimum of sample handling. The final analysis was performed with gas chromatography-mass spectrometry. Seven PCBs (28, 52, 101, 118, 138, 153 and 180) were analyzed, all of which are indicator congeners that, according to European legislation should be included in the analytical monitoring program. The extracted matrices were spiked feed for poultry and two certified reference materials naturally contaminated with PCBs (cod-liver oil and milk powder), which showed excellent conformity with certified data.

The Nordasvannet fjord in western Norway is a modern semi-enclosed basin suitable for studying sedimentary cycles as they occur under anoxic bottom conditions. It is characterized by strongly anoxic conditions in the water column and bottom sediments. Diagenetic pyrite formation occurs in the sediments, and syngenetic pyrite is formed in the lower water column. Organic matter burial in the fjord exceeds that of other environments with normal marine or upwelling conditions. This is due to the better preservation of organic matter. Organic matter composition appears to have changed over time with higher fractions of terrigenous organic matter being present in the most recent sediments. This may be a result of increased input of terrigenous organic matter, possibly due to sewage supply to the fjord over the last decades. Organic C and CaCO3 contents of the sediments do not appear to reflect a productivity signal. Calcium carbonate content is influenced by chemogenic calcite formation. Biogenic opal content appears to reflect a productivity signal, but different degrees of dissolution may obscure its clear recognition.

C/N ratios of organic matter sources in coastal lagoons and their drainage areas in the southern Baltic Sea region are investigated to determine the origin of organic matter (i.e. terrigenous or marine) in the sediments of the lagoons. These ratios are compared with δ13C values in the area. Terrestrial plants in the study area show C/N ratios between 10 and 85, whereas aquatic macrophytes have values in the range of 6 to 44. Peat and shore vegetation have C/N ratios between 15 and 16, and plankton shows values close to 6. In conjunction with δ13C values, the C/N ratios in the sediments allow the reconstruction of the Holocene palaeoenvironments and palaeoecology in the lagoons (Oder Estuary and Greifswalder Bodden). Distinct stages in the development of the water bodies, resulting from sea level changes in the region, can be derived: post-glacial lake stages with sandy sedimentation, lacustrine phases with high autochthonous productivity, terrestrial stages with peat formation, sedimentation as a result of marine transgression, and brackish sedimentation after the formation of sand spits and barrier islands. The application of Corg/Ntot ratios instead of Corg/Norg does not have any significant influence on the interpretation of the data and may thus be used in the coastal sediments of the southern Baltic Sea after having applied the test procedures presented in this study.

Organic carbon and nitrogen isotope values (δ13C, δ15N) and C/N ratios of six sediment cores from six coastal lagoons (including the Oder Estuary) were measured to chart the coastal development and to reconstruct the local palaeoenvironments of the southern Baltic Sea region during the Holocene. In addition, δ13C, δ15N and C/N values of major organic matter sources in the coastal lagoons and their drainage areas are investigated to determine the origin of organic matter (i.e. terrigenous or marine) in the sediments: plankton, aquatic macrophytes, typical C3 shore plants and peat. The δ13C, δ15N and C/N values of the samples collected show the clearly identifiable stages in the development of the water bodies: post-glacial lake stages with sandy sedimentation, lacustrine phases with high autochthonous productivity, terrestrial stages with peat formation, sedimentation as a result of marine transgression, and brackish sedimentation after the formation of sand spits and barrier islands. These stages are the results of sea level changes in the region. The values allow derivation of differences in the palaeoenvironments of the lagoons in the study area. A distinct terrestrial input is evident in the sediments of the lagoonal Oder Estuary, which can be attributed to the direct inflow of the Oder River into the lagoon. The isotope and C/N values also suggest a contribution of C4 plant detritus for the water bodies in the northeastern part of the study area (Barther Bodden, Grabow). The burial of autochthonous organic matter (i.e. plankton, aquatic macrophytes) in the sediment could be derived for all lagoons in this investigation.

The stability of vanillin in dairy products was investigated by means of highperformance liquid chromatography. While vanillin was oxidised to vanillic acid in fresh and pasteurised milk, it was stable in all other milk products investigated (UHT milk, pasteurised and UHT cream, yoghurt, curd and butter). The oxidation of vanillin to vanillic acid was shown to be pH-dependent. The relatively thermolabile enzyme xanthine oxidase was shown to be partly responsible for the formation of vanillic acid. However, peroxidase, which is also present in dairy products, did not lead to vanillic acid. Oxidation to the dimeric product, divanillin, occurred in the presence of peroxidase and hydrogen peroxide. The oxidation rate of synthetic vanillin to vanillic acid was very similar to that of vanillin from natural vanilla extracts or vanilla capsules. Both were shown to be stable in dairy products for subvention, such as butter and cream.