Genotype-based databases for variants causing rare diseases

Inherited diseases are the result of DNA sequence changes. In recessive diseases, the clinical phenotype results from the combined functional effects of variants in both copies of the gene. In some diseases there is often considerable variability of clinical presentation or disease severity, which may be predicted by the genotype. Additional effects may be triggered by environmental factors, as well as genetic modifiers which could be nucleotide polymorphisms in related genes, e.g. maternal ApoE or ABCA1 genotypes which may have an influence on the phenotype of SLOS individuals. Here we report the establishment of genotype variation databases for various rare diseases which provide individual clinical phenotypes associated with genotypes and include data about possible genetic modifiers. These databases aim to be an easy public access to information on rare and private variants with clinical data, which will facilitate the interpretation of genetic variants.     

Raised Middle-Finger: Electrocortical Correlates of Social Conditioning with Nonverbal Affective Gestures

Humans form impressions of others by associating persons (faces) with negative or positive social outcomes. This learning process has been referred to as social conditioning. In everyday life, affective nonverbal gestures may constitute important social signals cueing threat or safety, which therefore may support aforementioned learning processes. In conventional aversive conditioning, studies using electroencephalography to investigate visuocortical processing of visual stimuli paired with danger cues such as aversive noise have demonstrated facilitated processing and enhanced sensory gain in visual cortex. The present study aimed at extending this line of research to the field of social conditioning by pairing neutral face stimuli with affective nonverbal gestures. To this end, electro-cortical processing of faces serving as different conditioned stimuli was investigated in a differential social conditioning paradigm. Behavioral ratings and visually evoked steady-state potentials (ssVEP) were recorded in twenty healthy human participants, who underwent a differential conditioning procedure in which three neutral faces were paired with pictures of negative (raised middle finger), neutral (pointing), or positive (thumbs-up) gestures. As expected, faces associated with the aversive hand gesture (raised middle finger) elicited larger ssVEP amplitudes during conditioning. Moreover, theses faces were rated as to be more arousing and unpleasant. These results suggest that cortical engagement in response to faces aversively conditioned with nonverbal gestures is facilitated in order to establish persistent vigilance for social threat-related cues. This form of social conditioning allows to establish a predictive relationship between social stimuli and motivationally relevant outcomes.     

Private and collective interests; conflicts and solutions: the central theme of current thinking in evolutionary biology

The statement made by the population geneticist Theodosius Dobzhansky (1973): “Nothing in Biology Makes Sense Except in the Light of Evolution”, is often quoted as a crucially important generalization on the nature of biology. I am inclined to consider as equally important the statement: “Nothing in Evolutionary Biology Makes Sense Except in the Light of Conflicts between Parts and Systems.” This generalization takes account of the dynamic nature of biological phenomena, but also of the fact that the study of transitions from autonomous units to cooperative systems has become one of the most exciting and scientifically rewarding enterprises in all of organismic biology. The problems encountered and the speculations generated in the course of this enterprise will be either of the more unit-centered or of the more system-centered type, most biologists tending to lean towards one or the other. This explains why evolutionary biology is fraught with so many antagonistic attitudes and polarizing points of view. In this essay I want specifically to draw attention to and discuss the following issues which in recent years have polarized biologists: the dual nature of genes; the logic of Hamilton's rule; the relationship between kin selection, signalling networks and systemic manipulation; the semantic problem of progress in evolution; and the evolutionary consequences of the vastly differing time scales over which genotypic and phenotypic information processing occurs in higher animals.     

Consumer strategies of terrestrial gastropods and isopods

Summary Morphological, physiological and ecological evidence is used to show that terrestrial gastropods and isopods, although both can be considered as primary consumers, deal quite differently with the vegetabilic matter they use as food. Gastropods are both efficient digesters and assimilators whereas isopods are efficient digesters but usually inefficient assimilators. This combination may require the isopods to turn to coprophagy as a means of recovering some of the products of digestion that they had been unable to assimilate during the first passage of food through the gut. Furthermore, the faeces of isopods may contain dissolved nutrients and digestive enzymes that could be distributed through various routes of the food web of which these animals are parts.Supported by the Fonds zur Förderung der wissenschaftlichen Forschung in Österreich, project no. 2851     

Versatile analysis of single-molecule tracking data by comprehensive testing against Monte Carlo simulations

We propose here an approach for the analysis of single-molecule trajectories which is based on a comprehensive comparison of an experimental data set with multiple Monte Carlo simulations of the diffusion process. It allows quantitative data analysis, particularly whenever analytical treatment of a model is infeasible. Simulations are performed on a discrete parameter space and compared with the experimental results by a nonparametric statistical test. The method provides a matrix of p-values that assess the probability for having observed the experimental data at each setting of the model parameters. We show the testing approach for three typical situations observed in the cellular plasma membrane: i), free Brownian motion of the tracer, ii), hop diffusion of the tracer in a periodic meshwork of squares, and iii), transient binding of the tracer to slowly diffusing structures. By plotting the p-value as a function of the model parameters, one can easily identify the most consistent parameter settings but also recover mutual dependencies and ambiguities which are difficult to determine by standard fitting routines. Finally, we used the test to reanalyze previous data obtained on the diffusion of the glycosylphosphatidylinositol-protein CD59 in the plasma membrane of the human T24 cell line.     

UniProtJAPI: a remote API for accessing UniProt data

Programmatic access to the UniProt Knowledgebase (UniProtKB) is essential for many bioinformatics applications dealing with protein data. We have created a Java library named UniProtJAPI, which facilitates the integration of UniProt data into Java-based software applications. The library supports queries and similarity searches that return UniProtKB entries in the form of Java objects. These objects contain functional annotations or sequence information associated with a UniProt entry. Here, we briefly describe the UniProtJAPI and demonstrate its usage.     

Ozone uptake in the sun and shade crown of spruce: quantifying the physiological effects of ozone exposure

Summary The uptake of air pollutants depends both on pollutant concentration and on stomatal conductance. This paper deals with the uptake of ozone (O₃) from the air into the needles of Norway spruce [Picea abies (L.) Karst.] under ambient climatic conditions. Regulation of O₃ uptake by the stomata is shown and also the difference between the physiologically active O₃ concentration and the O₃ concentration of the ambient air. Data from the sun and shade crown of spruce trees at 1000 m a.s.l. are presented. Analysis of data from three vegetation periods has shown that at low ambient O₃ concentrations the O₃ uptake is largely regulated by stomatal conductance. Water vapour pressure deficit (VPD) of the atmosphere is the climatic factor which showed the highest positive correlation with O₃ concentration. However, a high leaf-air VDP led to stomatal closure, thus reducing the O₃ uptake in the needles despite high O₃ concentrations in the ambient air. The potential O₃ stress caused by high O₃ concentrations can be strongly mitigated by this natural closing of the stomata and the simultaneous occurrence of moderate drought stress.