A detailed phenotypic analysis of immune cell populations in the bronchoalveolar lavage fluid of atopic asthmatics after segmental allergen challenge

BACKGROUND: Atopic asthma is characterized by intermittent exacerbations triggered by exposure to allergen. Exacerbations are characterized by an acute inflammatory reaction in the airways, with recruitment of both innate and adaptive immune cells. These cell populations as well as soluble factors are critical for initiating and controlling the inflammatory processes in allergic asthma. Detailed data on the numbers and types of cells recruited following allergen challenge is lacking. In this paper we present an extensive phenotypic analysis of the inflammatory cell infiltrate present in the bronchoalveolar lavage (BAL) fluid following bronchoscopically directed allergen challenge in mild atopic asthmatics. METHODS: A re-analysis of pooled data obtained prior to intervention in our randomized, placebo controlled, double blinded study (costimulation inhibition in asthma trial [CIA]) was performed. Twenty-four subjects underwent bronchoscopically directed segmental allergen challenge followed by BAL collection 48 hours later. The BAL fluid was analyzed by multi-color flow cytometry for immune cell populations and multi-plex ELISA for cytokine detection. RESULTS: Allergen instillation induced pro-inflammatory cytokines (IL-6) and immune modulating cytokines (IL-2, IFN-γ, and IL-10) along with an increase in lymphocytes and suppressor cells (Tregs and MDSC). Interestingly, membrane expression of CD30 was identified on lymphocytes, especially Tregs, but not eosinophils. Soluble CD30 was also detected in the BAL fluid after allergen challenge in adult atopic asthmatics. CONCLUSIONS: After segmental allergen challenge of adult atopic asthmatics, cell types associated with a pro-inflammatory as well as an anti-inflammatory response are detected within the BAL fluid of the lung

A format for phylogenetic placements

We have developed a unified format for phylogenetic placements, that is, mappings of environmental sequence data (e.g. short reads) into a phylogenetic tree. We are motivated to do so by the growing number of tools for computing and post-processing phylogenetic placements, and the lack of an established standard for storing them. The format is lightweight, versatile, extensible, and is based on the JSON format which can be parsed by most modern programming languages. Our format is already implemented in several tools for computing and post-processing parsimony- and likelihood-based phylogenetic placements, and has worked well in practice. We believe that establishing a standard format for analyzing read placements at this early stage will lead to a more efficient development of powerful and portable post-analysis tools for the growing applications of phylogenetic placement.Comment: Documents version 3 of the forma

Small mirrors do the trick: A simple, but effective method to study mirror self-recognition in chimpanzees

Mirror self-recognition (MSR) is considered an indicator of self-awareness. Standardized mirror tests reveal compelling evidence for MSR in a few non-human species, including all great apes. However, substantial inter-individual variation of MSR within species resulted in an ongoing methodological controversy, questioning the appropriateness of standard MSR tests for cross-species comparisons. Lack of motivation, in particular, is discussed as one possible cause for false negative results. Here, we compare the spontaneous behavioral response of 47 zoo-housed chimpanzees (Pan troglodytes) to (i) standard body-sized, stationary mirrors and (ii) small, portable hand mirrors. We predicted that the monopolizability and maneuverability of small mirrors increase the chances of identifying MSR across a larger proportion of individuals. Chimpanzees both revealed a substantially higher frequency of general mirror-related behaviors and engaged in significantly more and longer behaviors specifically indicating MSR when provided with small mirrors compared to a large mirror. Handheld mirrors provide a more sensitive measure for MSR within and likely between primate species than the traditional large mirrors, and thereby are a potentially valuable tool for studying self-awareness across species

Genome-wide linkage screen for testicular germ cell tumour susceptibility loci

A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the diseas

The application of high temporal resolution data in river catchment modelling and management strategies

Modelling changes in river water quality, and by extension developing river management strategies, has historically been reliant on empirical data collected at relatively low temporal resolutions. With access to data collected at higher temporal resolutions, this study investigated how these new dataset types could be employed to assess the precision and accuracy of two phosphorus (P) load apportionment models (LAMs) developed on lower resolution empirical data. Predictions were made of point and diffuse sources of P across ten different sampling scenarios. Sampling resolution ranged from hourly to monthly through the use of 2000 newly created datasets from high frequency P and discharge data collected from a eutrophic river draining a 9.48 km2 catchment. Outputs from the two LAMs were found to differ significantly in the P load apportionment (51.4% versus 4.6% from point sources) with reducing precision and increasing bias as sampling frequency decreased. Residual analysis identified a large deviation from observed data at high flows. This deviation affected the apportionment of P from diffuse sources in particular. The study demonstrated the potential problems in developing empirical models such as LAMs based on temporally relatively poorly-resolved data (the level of resolution that is available for the majority of catchments). When these models are applied ad hoc and outside an expert modelling framework using extant datasets of lower resolution, interpretations of their outputs could potentially reduce the effectiveness of management decisions aimed at improving water quality

Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery.

BACKGROUND/OBJECTIVES: Bariatric surgery offers sustained marked weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear. SUBJECTS/METHODS: We mapped the coordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. RESULTS: The response of circulating microRNAs (miRNAs) to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signaling pathways including G protein signaling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, tricarboxylic acid cycle, pentose phosphate shunt, fatty-acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. CONCLUSIONS: The close association between energy metabolism, neuronal signaling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting

Differing views - can chimpanzees do level 2 perspective-taking?

We gratefully acknowledge financial support by the German National Academic Foundation.Although chimpanzees understand what others may see, it is unclear if they understand how others see things (Level 2 perspective-taking). We investigated whether chimpanzees can predict the behavior of a conspecific which is holding a mistaken perspective that differs from their own. The subject competed with a conspecific over two food sticks. While the subject could see that both were the same size, to the competitor one appeared bigger than the other. In a previously established game, the competitor chose one stick in private first and the subject chose thereafter, without knowing which of the sticks was gone. Chimpanzees and 6-year-old children chose the ‘riskier’ stick (that looked bigger to the competitor) significantly less in the game than in a nonsocial control. Children chose randomly in the control, thus showing Level 2 perspective-taking skills; in contrast, chimpanzees had a preference for the ‘riskier’ stick here, rendering it possible that they attributed their own preference to the competitor to predict her choice. We thus run a follow-up in which chimpanzees did not have a preference in the control. Now they also chose randomly in the game. We conclude that chimpanzees solved the task by attributing their own preference to the other, while children truly understood the other’s mistaken perspective.Publisher PDFPeer reviewe

Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge, the first analysis of the X chromosome. Eight new loci mapping to 2q14.2, 3q26.2, 4q35.2, 7q36.3, 10q26.13, 15q21.3, 15q22.31, and Xq28 achieved genome-wide significance (P < 5 × 10−8). Most loci harbor biologically plausible candidate genes. We refined previously reported associations at 9p24.3 and 19p12 by identifying one and three additional independent SNPs, respectively. In aggregate, the 39 independent markers identified to date explain 37% of father-to-son familial risk, 8% of which can be attributed to the 12 new signals reported here. Our findings substantially increase the number of known TGCT susceptibility alleles, move the field closer to a comprehensive understanding of the underlying genetic architecture of TGCT, and provide further clues to the etiology of TGCT