Minimalistic Peptide-Based Supramolecular Systems Relevant to the Chemical Origin of Life

All forms of life are based on biopolymers, which are made up of a selection of simple building blocks, such as amino acids, nucleotides, fatty acids and sugars. Their individual properties govern their interactions, giving rise to complex supramolecular structures with highly specialized functionality, including ligand recognition, catalysis and compartmentalization. In this thesis, we aim to answer the question whether short peptides could have acted as precursors of modern proteins during prebiotic evolution. Using a combination of experimental and computational techniques, we screened a large molecular search space for peptide sequences that are capable of forming supramolecular complexes with adenosine triphosphate (ATP), life’s ubiquitous energy currency, and uridine triphosphate (UTP). Our results demonstrate that peptides as short as heptamers can form dynamic supramolecular complexes, adapt their structure to a ligand upon binding, undergo phase-separation into spatially confined compartments and catalyze nucleotide-hydrolysis

Quantifying alternative splicing from paired-end RNA-sequencing data

RNA-sequencing has revolutionized biomedical research and, in particular, our ability to study gene alternative splicing. The problem has important implications for human health, as alternative splicing may be involved in malfunctions at the cellular level and multiple diseases. However, the high-dimensional nature of the data and the existence of experimental biases pose serious data analysis challenges. We find that the standard data summaries used to study alternative splicing are severely limited, as they ignore a substantial amount of valuable information. Current data analysis methods are based on such summaries and are hence suboptimal. Further, they have limited flexibility in accounting for technical biases. We propose novel data summaries and a Bayesian modeling framework that overcome these limitations and determine biases in a nonparametric, highly flexible manner. These summaries adapt naturally to the rapid improvements in sequencing technology. We provide efficient point estimates and uncertainty assessments. The approach allows to study alternative splicing patterns for individual samples and can also be the basis for downstream analyses. We found a severalfold improvement in estimation mean square error compared popular approaches in simulations, and substantially higher consistency between replicates in experimental data. Our findings indicate the need for adjusting the routine summarization and analysis of alternative splicing RNA-seq studies. We provide a software implementation in the R package casper.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS687 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org). With correction

Regional Rarity: Consequences of Dispersal Limitation and Strategies for Reintroduction

Understanding factors that limit species distributions within restored habitats has been a longstanding goal of restoration ecology, particularly with respect to differences between rare and widespread species. Numerous mechanisms have been proposed to contribute to rarity, including species traits, propagule limitation, ecological requirements, and population level processes such as demographic and environmental stochasticity. Yet, our understanding of species rarity remains limited since few studies have examined how these factors act in concert. This dissertation examines how these mechanisms may interact to influence the distribution and population establishment of plant species in restored xeric glades in the Missouri Ozarks: USA). First, I used a trait analysis of species in restored glades to determine whether traits related to niche breadth, persistence, or dispersal ability are related to species distributions. The results from this study suggest that several traits may interact to allow species to become widespread in this restored xeric habitat, including habitat specialization of open canopy environments, perennial or clonal life histories, and adaptations to arid conditions such as short plant height. To follow up these observations, I experimentally tested the degree to which propagule limitation, competitive environment: competitors present, burned, or removed), and abiotic stress: precipitation of typical dry, average and wet years) differentially limit the seedling establishment of 32 rare versus widespread species. I found that rare species established as well as widespread species in all treatments, suggesting that dispersal, rather than differences in stress tolerance or competitive ability, is the predominant limiting force for species distributions. This suggests that propagule introductions may be sufficient to increase rare species distributions. To examine how the success of propagule introduction might be influenced by propagule pressure: i.e., a single large versus several small introductions) versus habitat management during introduction: i.e., creating favorable conditions for seedling establishment), I conducted a meta-analysis with demographic modeling. My results indicate that habitat management during introduction has a much greater effect on long-term population establishment compared to propagule pressure. In summary, this dissertation demonstrates the importance of dispersal for limiting species distributions in restored habitats and also provides recommendations on how to best reintroduce rare species

Use of human protein C concentrates in the treatment of patients with severe congenital protein C deficiency

Protein C is one of the major inhibitors of the coagulation system that downregulate thrombin generation. Severe congenital protein C deficiency leads to a hypercoagulability state that usually presents at birth with purpura fulminans and/or severe venous and arterial thrombosis. Recurrent thrombotic events are commonly seen. From the 1990’s, several virus-inactivated human protein C concentrates have been developed. These concentrates currently constitute the therapy of choice for the treatment and prevention of clinical manifestations of severe congenital protein C deficiency. This review summarizes the available information on the use of human protein C concentrates in patients with severe congenital protein C deficiency

The odor of origin: kinship and geographical distance are reflected in the marking pheromone of male beewolves (Philanthus triangulum F., Hymenoptera, Crabronidae)

<p>Abstract</p> <p>Background</p> <p>Pheromones play an important role for mate finding and courtship in many insects. In species where males are the signaling sex, females are expected to choose among potential mates with regard to the emitter's quality and/or genetic compatibility. One important aspect is the balance between negative and positive effects of in- vs. outbreeding. In the present study, we aimed to assess the potential of the territory marking pheromone of European beewolves as an indicator for genetic compatibility in the context of female choice.</p> <p>Results</p> <p>We analyzed the sex pheromone composition of male European beewolves (<it>Philanthus triangulum </it>F., Hymenoptera, Crabronidae) from eight different locations across Central Europe (six in Germany, one in England, and one in Italy). The pheromone constitutes a complex blend of various long-chain hydrocarbons (alkanes, alkenes, alcohols, ketones, and a carbon acid). We demonstrate that pheromone composition differs significantly among distant populations (regional scale), among subpopulations (local scale) and between families within subpopulations. The differences in the pheromone blend are positively correlated with geographical distances as might be expected according to an isolation-by-distance model. On a local scale, family membership has a larger effect on pheromone composition than subpopulation affiliation, while the reverse is true for the regional scale.</p> <p>Conclusion</p> <p>Our results show that male pheromones can contain information on both kinship and geographical origin that may be used by females to choose adaptively among potential mates on the basis of their genetic distance.</p