Biology subjects

Schmidt, J.

Publications and source records attributed to Schmidt, J..

78 records · Page 5Linked to original sources

bioRxiv2019

Nociception testing duringfixed-wing ambulance flights.An interventional pilot study on the effects of flight-related environmental changes on the nociception of healthy volunteers.

BackgroundThe effects of environmental changes on the somato-sensory system during long-distance air ambulance flights need to be further investigated. Changes in nociceptive capacity are conceivable in light of previous studies performed under related environmental settings. We used standardized somato-sensory testing to investigate nociception in healthy volunteers during air-ambulance flights.\n\nMethodsTwenty-five healthy individuals were submitted to a test compilation analogous to the quantitative sensory testing battery - performed during actual air-ambulance flights. Measurements were paired around the major changes of external factors during take-off/climb and descent/landing. Bland-Altman-Plots were calculated to identify possible systemic effects.\n\nResultsBland-Altman-analyses suggest that the thresholds of stimulus detection and pain as well as above-threshold pain along critical waypoints of travel are not subject to systemic effects but instead demonstrate random variations.\n\nConclusionsWe provide a novel description of a real-life experimental setup and demonstrate the general feasibility of performing somato-sensory testing during ambulance flights. No systematic effects on the nociception of healthy individuals were apparent from our data. Our findings open up the possibility of future investigations into potential effects of ambulance flights on patients suffering acute or chronic pain.

physiology↗

bioRxiv2018

A New Method to Correct for Habitat Filtering in Microbial Correlation Networks

Amplicon sequencing of 16S, ITS, and 18S regions of microbial genomes is a commonly used first step toward understanding microbial communities of interest for human health, agriculture, and the environment. Correlation network analysis is an emerging tool for investigating the interactions within these microbial communities. However, when data from different habitats (e.g sampling sites, host genotype, etc.) are combined into one analysis, habitat filtering (co-occurrence of microbes due to habitat sampled rather than biological interactions) can induce apparent correlations, resulting in a network dominated by habitat effects and masking correlations of biological interest. We developed an algorithm to correct for habitat filtering effects in microbial correlation network analysis in order to reveal the true underlying microbial correlations. This algorithm was tested on simulated data that was constructed to exhibit habitat filtering. Our algorithm significantly improved correlation detection accuracy for these data compared to Spearman and Pearson correlations. We then used our algorithm to analyze a real data set of 16S-V4 amplicon sequences that was expected to exhibit habitat filtering. Our algorithm was found to effectively reduce habitat effects, enabling the construction of consensus correlation networks from data sets combining multiple related sample habitats.

bioinformatics↗

bioRxiv2018

A structure-based approach towards identification of inhibitory fragments for eleven-nineteen-leukemia protein (ENL) YEATS domain

Lysine acetylation is an epigenetic mark that is principally recognized by bromodomains and recently structurally diverse YEATS domains also emerged as readers of lysine acetyl/acylations. Here we present a crystallography-based strategy and the discovery of fragments binding to the ENL YEATS domain, a potential drug target. Crystal structures combined with synthetic efforts led to the identification of a sub-micromolar binder, providing first starting points for the development of chemical probes for this reader domain family.

biochemistry↗

bioRxiv2017

The C-terminal extension landscape of naturally presented HLA-I ligands

HLA-I molecules play a central role in antigen presentation. They typically bind 9- to 12-mer peptides and their canonical binding mode involves anchor residues at the second and last positions of their ligands. To investigate potential non-canonical binding modes we collected in-depth and accurate HLA peptidomics datasets covering 54 HLA-I alleles and developed novel algorithms to analyze these data. Our results reveal frequent (442 unique peptides) and statistically significant C-terminal extensions for at least eight alleles, including the common HLA-A03:01, HLA-A31:01 and HLA-A68:01. High resolution crystal structure of HLA-A68:01 with such a ligand uncovers structural changes taking place to accommodate C-terminal extensions and helps unraveling sequence and structural properties predictive of the presence of these extensions. Scanning viral proteomes with the new C-terminal extension motifs identifies many putative epitopes and we demonstrate direct recognition by human CD8+ T cells of a C-terminally extended epitope from cytomegalovirus.

immunology↗

bioRxiv2017

The Kobresia pygmaea ecosystem of the Tibetan highlands – origin, functioning and degradation of the world’s largest pastoral alpine ecosystem

Kobresia pastures in the eastern Tibetan highlands occupy 450000 km2 and form the worlds largest pastoral alpine ecosystem. The main constituent is an endemic dwarf sedge, Kobresia pygmaea, which forms a lawn with a durable turf cover anchored by a felty root mat, and occurs from 3000 m to nearly 6000 m a.s.l. The existence and functioning of this unique ecosystem and its turf cover have not yet been explained against a backdrop of natural and anthropogenic factors, and thus its origin, drivers, vulnerability or resilience remain largely unknown. Here we present a review on ecosystem diversity, reproduction and ecology of the key species, pasture health, cycles of carbon (C), water and nutrients, and on the paleo-environment. The methods employed include molecular analysis, grazing exclusion, measurements with micro-lysimeters and gas exchange chambers, 13C and 15N labelling, eddy-covariance flux measurements, remote sensing and atmospheric modelling.\n\nThe following combination of traits makes Kobresia pygmaea resilient and highly competitive: dwarf habit, predominantly below-ground allocation of photo assimilates, mixed reproduction strategy with both seed production and clonal growth, and high genetic diversity. Growth of Kobresia pastures is co-limited by low rainfall during the short growing season and livestock-mediated nutrient withdrawal. Overstocking has caused pasture degradation and soil deterioration, yet the extent remains debated. In addition, we newly describe natural autocyclic processes of turf erosion initiated through polygonal cracking of the turf cover, and accelerated by soil-dwelling endemic small mammals. The major consequences of the deterioration of the vegetation cover and its turf include: (1) the release of large amounts of C and nutrients and (2) earlier diurnal formation of clouds resulting in (3) decreased surface temperatures with (4) likely consequences for atmospheric circulation on large regional and, possibly global, scales.\n\nPaleo-environmental reconstruction, in conjunction with grazing experiments, suggests that the present grazing lawns of Kobresia pygmaea are synanthropic and may have existed since the onset of pastoralism. The traditional migratory rangeland management was sustainable over millennia and possibly still offers the best strategy to conserve, and possibly increase, the C stocks in the Kobresia turf, as well as its importance for climate regulation.

ecology↗

bioRxiv2017

Signatures of long-term balancing selection in human genomes

Balancing selection maintains advantageous diversity in populations through various mechanisms. While extensively explored from a theoretical perspective, an empirical understanding of its prevalence and targets lags behind our knowledge of positive selection. Here we describe the Non-Central Deviation (NCD), a simple yet powerful statistic to detect long-term balancing selection (LTBS) that quantifies how close frequencies are to expectations under LTBS, and provides the basis for a neutrality test. NCD can be applied to a single locus or genomic data, and can be implemented considering only polymorphisms (NCD1) or also considering fixed differences with respect to an outgroup (NCD2) species. Incorporating fixed differences improves power, and NCD2 has higher power to detect LTBS in humans under different frequencies of the balanced allele(s) than other available methods. Applied to genome-wide data from African and European human populations, in both cases using chimpanzee as an outgroup, NCD2 shows that, albeit not prevalent, LTBS affects a sizable portion of the genome: about 0.6% of analyzed genomic windows and 0.8% of analyzed positions. Significant windows (p < 0.0001) contain 1.6% of SNPs in the genome, which disproportionally fall within exons and change protein sequence, but are not enriched in putatively regulatory sites. These windows overlap about 8% of the protein-coding genes, and these have larger number of transcripts than expected by chance even after controlling for gene length. Our catalog includes known targets of LTBS but a majority of them (90%) are novel. As expected, immune-related genes are among those with the strongest signatures, although most candidates are involved in other biological functions, suggesting that LTBS potentially influences diverse human phenotypes.

genomics↗