Steinar Thorvaldsen

Molecular characterization of cold adaptation based on ortholog protein sequences from Vibrionaceae species

A set of 298 protein families from psychrophilic Vibrio salmonicida was compiled to identify genotypic characteristics that discern it from orthologous sequences from the mesophilic Vibrio/Photobacterium branch of the gamma-Proteobacteria (Vibrionaceae family). In our comparative exploration we employed alignment based bioinformatical and statistical methods. Interesting information was found in the substitution matrices, and the pattern of asymmetries in the amino acid substitution process. Together with the compositional difference, they identified the amino acids Ile, Asn, Ala and Gln as those having the most psycrophilic involvement. Ile and Asn are enhanced whereas Gln and Ala are suppressed. The inflexible Pro residue is also suppressed in loop regions, as expected in a flexible structure. The dataset were also classified and analysed according to the predicted subcellular location, and we made an additional study of 183 intracellular and 65 membrane proteins. Our results revealed that the psychrophilic proteins have similar hydrophobic and charge contributions in the core of the protein as mesophilic proteins, while the solvent-exposed surface area is significantly more hydrophobic. In addition, the psychrophilic intracellular (but not the membrane) proteins are significantly more negatively charged at the surface. Our analysis supports the hypothesis of preference for more flexible amino acids at the molecular surface. Life in cold climate seems to be obtained through many minor structural modifications rather than certain amino acids substitutions.

DeltaProt: a software toolbox for comparative genomics

BackgroundStatistical bioinformatics is the study of biological data sets obtained by new micro-technologies by means of proper statistical methods. For a better understanding of environmental adaptations of proteins, orthologous sequences from different habitats may be explored and compared. The main goal of the DeltaProt Toolbox is to provide users with important functionality that is needed for comparative screening and studies of extremophile proteins and protein classes. Visualization of the data sets is also the focus of this article, since visualizations can play a key role in making the various relationships transparent. This application paper is intended to inform the reader of the existence, functionality, and applicability of the toolbox.ResultsWe present the DeltaProt Toolbox, a software toolbox that may be useful in importing, analyzing and visualizing data from multiple alignments of proteins. The toolbox has been written in MATLAB™ to provide an easy and user-friendly platform, including a graphical user interface, while ensuring good numerical performance. Problems in genome biology may be easily stated thanks to a compact input format. The toolbox also offers the possibility of utilizing structural information from the SABLE or other structure predictors. Different sequence plots can then be viewed and compared in order to find their similarities and differences. Detailed statistics are also calculated during the procedure.ConclusionsThe DeltaProt package is open source and freely available for academic, non-commercial use. The latest version of DeltaProt can be obtained from http://services.cbu.uib.no/software/deltaprot/. The website also contains documentation, and the toolbox comes with real data sets that are intended for training in applying the models to carry out bioinformatical and statistical analyses of protein sequences.Equipped with the new algorithms proposed here, DeltaProt serves as an auxiliary analysis tool capable of visualizing and comparing orthologus protein sequences. The framework of the algorithms also enables easy incorporation of extra information on structure, if such data is available.

Molecular Characterization of Cold Adaptation of Membrane Proteins in the Vibrionaceae Core-Genome

Cold-adaptation strategies have been studied in multiple psychrophilic organisms, especially for psychrophilic enzymes. Decreased enzyme activity caused by low temperatures as well as a higher viscosity of the aqueous environment require certain adaptations to the metabolic machinery of the cell. In addition to this, low temperature has deleterious effects on the lipid bilayer of bacterial membranes and therefore might also affect the embedded membrane proteins. Little is known about the adaptation of membrane proteins to stresses of the cold. In this study we investigate a set of 66 membrane proteins from the core genome of the bacterial family Vibrionaceae to identify general characteristics that discern psychrophilic and mesophilic membrane proteins. Bioinformatical and statistical methods were used to analyze the alignments of the three temperature groups mesophilic, intermediate and psychrophilic. Surprisingly, our results show little or no adaptation to low temperature for those parts of the proteins that are predicted to be inside the membrane. However, changes in amino acid composition and hydrophobicity are found for complete sequences and sequence parts outside the lipid bilayer. Among others, the results presented here indicate a preference for helix-breaking and destabilizing amino acids Ile, Asp and Thr and an avoidance of the helix-forming amino acid Ala in the amino acid composition of psychrophilic membrane proteins. Furthermore, we identified a lower overall hydrophobicity of psychrophilic membrane proteins in comparison to their mesophilic homologs. These results support the stability-flexibility hypothesis and link the cold-adaptation strategies of membrane proteins to those of loop regions of psychrophilic enzymes.

There are more small amino acids and fewer aromatic rings in proteins of ionizing radiation-resistant bacteria

The identification of specific amino acids (AAs) or groups of functionally important AA residues in ionizing radiation-resistant bacteria (IRRB) is an important challenge in understanding the biological basis of resistance to ionizing radiation (IR; X-rays and gamma-rays). To address this problem, we compared homologous sites in multiple alignments of proteins of IRRB and IR-sensitive bacteria (IRSB) using the DeltaProt Toolbox. Substitution patterns were used as evidence for selection of certain AAs over others. Our results show that, in contrast to aromatic AAs, small/tiny AAs tend to be preferred in IRRB compared to IRSB. In agreement with previous experimental data showing that oxidation of AA residues is causative in the killing of irradiated cells and that IR resistance is correlated with the accumulation of divalent manganese ions (Mn2+)–peptide–orthophosphate (Pi) complexes, we proposed a chemical interpretation based on the Hard and Soft (Lewis) Acids and Bases (HSAB) concept. These findings should assist future efforts in selecting mutations for rational design of proteins with enhanced IR tolerance properties.

Teaching Logic through Web-Based and Gamified Quizzing of Formal Arguments

In this paper the focus is on the construction, use, pedagogical potential, and long-term sustainability of certain web-based tools designed for teaching logic. A series of web-based tools have been implemented as a two-part system, and the tools have been tested and evaluated in a number of practical experiments. The first part of the system is a student-facing Java-Applet running in the students browser, implemented using the Prolog programming language as embodied in a Java implementation called Prolog+CG. The second part is a teacher-oriented, server-based backend for logging the progress of students. In the paper, we provide a presentation of the pedagogical and technical ideas of construction that underpin the tools which have been made so far. It is explained how the tools can be developed as web applications using gamified quizzing. We then provide an evaluation of the potential of log data as learning analytics offered by these tools in the context of university courses introducing basic logic and formal aspects of argumentation. We also describe how we have used and evaluated the tools in a real learning context, using both quantitative, log-based data and qualitative interview. The evaluation also includes a discussion of the ethical aspects concerning the logging of student data. We also provide some insights on how the tools can and have been made sustainable.

Property-Dependent Analysis of Aligned Proteins from Two Or More Populations.

Multiple sequence alignments can provide information for comparative analyses of proteins and protein populations. We present some statistical trend-tests that can be used when an aligned data set can be divided into two or more populations based on phenotypic traits such as preference of temperature, pH, salt concentration or pressure. The approach is based on estimation and analysis of the variation between the values of physicochemical parameters at positions of the sequence alignment. Monotonic trends are detected by applying a cumulative Mann-Kendall test. The method is found to be useful to identify significant physicochemical mechanisms behind adaptation to extreme environments and uncover molecular differences between mesophile and extremophile organisms. A filtering technique is also presented to visualize the underlying structure in the data. All the comparative statistical methods are available in the toolbox DeltaProt.

Classical Syllogisms in Logic Teaching

This paper focuses on the challenges of introducing classical syllogisms in university courses in elementary logic and human reasoning. Using a program written in Prolog+CG, some empirical studies have been carried out involving three groups of students in Denmark; one group of philosophy students and two groups of students of informatics. The skills of the students in syllogistic reasoning before and after the logic courses have been studied and are discussed. The empirical observations made with the program make it possible to identify syllogisms which are found difficult by the students, and to identify others which the students find easier to handle. It is discussed why certain syllogisms are more difficult than others to assess correctly with respect to validity. The results are compared with findings from earlier studies in the literature. As in other studies, it is shown that the test persons have a tendency correctly to assess valid syllogisms as such more often than correctly assessing invalid syllogisms as such. It is also investigated to what extent the students have improved their skills in practical reasoning by attending the logic courses. Finally, some open questions regarding syllogistic reasoning are discussed.

The Impact of Cyberbullying and Cyber Harassment on Academic Achievement

Bullying is often seen as a subcategory of peer aggression. Three criteria distinguish bullying from other kinds of aggression: imbalance of power, repetition or duration of negative actions and a deliberate will to hurt. Research was initially directed towards physical and verbal forms of harassment (Olweus, 2001; Heinemann, 1973; Olweus, 1978).

Teaching Syllogistics Using Conceptual Graphs

It has for centuries been commonly believed that syllogistic reasoning is an essential part of human rationality. For this reason, Aristotelian syllogistics has since the rise of the European university been a standard component of logic teaching. During the medieval period syllogistic validity was presented in terms of a number of artificial words designed to summarize the deductive structure of this basic system. The present paper is a continuation of earlier studies involving practical experiments with informatics students using a student-facing Java-Applet running in the student’s browser, implemented using the Prolog programming language as embodied in a Java implementation called Prolog+CG. The aim of the present paper is to study some interesting conceptual aspects of syllogistic reasoning and to investigate whether CG formalism can be helpful in order to obtain a better understanding of syllogistic reasoning in general and the system of Aristotelian syllogisms conceived as a deductive (axiomatic) structure in particular. Some prototypes of tools for basic logic teaching have been developed using Prolog+CG, and various preliminary tests of the tools have been carried out.

Exact Markov chains versus diffusion theory for haploid random mating.

Exact discrete Markov chains are applied to the Wright-Fisher model and the Moran model of haploid random mating. Selection and mutations are neglected. At each discrete value of time t there is a given number n of diploid monoecious organisms. The evolution of the population distribution is given in diffusion variables, to compare the two models of random mating with their common diffusion limit. Only the Moran model converges uniformly to the diffusion limit near the boundary. The Wright-Fisher model allows the population size to change with the generations. Diffusion theory tends to under-predict the loss of genetic information when a population enters a bottleneck.