Biomolecular network motif counting and discovery by color coding

Protein-protein interaction (PPI) networks of many organisms share global topological features such as degree distribution, k-hop reachability, betweenness and closeness. Yet, some of these networks can differ significantly from the others in terms of local structures: e.g. the number of specific network motifs can vary significantly among PPI networks. Counting the number of network motifs provides a major challenge to compare biomolecular networks. Recently developed algorithms have been able to count the number of induced occurrences of subgraphs with k < or = 7 vertices. Yet no practical algorithm exists for counting non-induced occurrences, or counting subgraphs with k > or = 8 vertices. Counting non-induced occurrences of network motifs is not only challenging but also quite desirable as available PPI networks include several false interactions and miss many others. In this article, we show how to apply the 'color coding' technique for counting non-induced occurrences of subgraph topologies in the form of trees and bounded treewidth subgraphs. Our algorithm can count all occurrences of motif G' with k vertices in a network G with n vertices in time polynomial with n, provided k = O(log n). We use our algorithm to obtain 'treelet' distributions for k < or = 10 of available PPI networks of unicellular organisms (Saccharomyces cerevisiae Escherichia coli and Helicobacter Pyloris), which are all quite similar, and a multicellular organism (Caenorhabditis elegans) which is significantly different. Furthermore, the treelet distribution of the unicellular organisms are similar to that obtained by the 'duplication model' but are quite different from that of the 'preferential attachment model'. The treelet distribution is robust w.r.t. sparsification with bait/edge coverage of 70% but differences can be observed when bait/edge coverage drops to 50%.     

A possible mechanism for self-coordination of bidirectional traffic across nuclear pores

Nuclear pore complexes are constantly confronted by large fluxes of macromolecules and macromolecular complexes that need to get into and out of the nucleus. Such bidirectional traffic occurring in a narrow channel can easily lead to jamming. How then is passage between the nucleus and cytoplasm maintained under the varying conditions that arise during the lifetime of the cell? Here, we address this question using computer simulations in which the behaviour of the ensemble of transporting cargoes is analysed under different conditions. We suggest that traffic can exist in two distinct modes, depending on the concentration of cargoes and dissociation rates of the transport receptor-cargo complexes from the pores. In one mode, which prevails when dissociation is quick and cargo concentration is low, transport in either direction proceeds uninterrupted by transport in the other direction. The result is that the overall traffic direction fluctuates rapidly and unsystematically between import and export. Remarkably, when cargo concentrations are high and disassociation is slow, another mode takes over in which traffic proceeds in one direction for a certain extent of time, after which it flips direction for another period. The switch between this, more regulated, mode of transport and the other, quickly fluctuating state, does not require an active gating mechanism but rather occurs spontaneously through the dynamics of the transported particles themselves. The determining factor for the behaviour of traffic is found to be the exit rate from the pore channel, which is directly related to the activity of the Ran system that controls the loading and release of cargo in the appropriate cellular compartment.     

Facilitated variation: how evolution learns from past environments to generalize to new environments

One of the striking features of evolution is the appearance of novel structures in organisms. Recently, Kirschner and Gerhart have integrated discoveries in evolution, genetics, and developmental biology to form a theory of facilitated variation (FV). The key observation is that organisms are designed such that random genetic changes are channeled in phenotypic directions that are potentially useful. An open question is how FV spontaneously emerges during evolution. Here, we address this by means of computer simulations of two well-studied model systems, logic circuits and RNA secondary structure. We find that evolution of FV is enhanced in environments that change from time to time in a systematic way: the varying environments are made of the same set of subgoals but in different combinations. We find that organisms that evolve under such varying goals not only remember their history but also generalize to future environments, exhibiting high adaptability to novel goals. Rapid adaptation is seen to goals composed of the same subgoals in novel combinations, and to goals where one of the subgoals was never seen in the history of the organism. The mechanisms for such enhanced generation of novelty (generalization) are analyzed, as is the way that organisms store information in their genomes about their past environments. Elements of facilitated variation theory, such as weak regulatory linkage, modularity, and reduced pleiotropy of mutations, evolve spontaneously under these conditions. Thus, environments that change in a systematic, modular fashion seem to promote facilitated variation and allow evolution to generalize to novel conditions.     

Transient induced gamma-band response in EEG as a manifestation of miniature saccades

The induced gamma-band EEG response (iGBR) recorded on the scalp is widely assumed to reflect synchronous neural oscillation associated with object representation, attention, memory, and consciousness. The most commonly reported EEG iGBR is a broadband transient increase in power at the gamma range approximately 200-300 ms following stimulus onset. A conspicuous feature of this iGBR is the trial-to-trial poststimulus latency variability, which has been insufficiently addressed. Here, we show, using single-trial analysis of concomitant EEG and eye tracking, that this iGBR is tightly time locked to the onset of involuntary miniature eye movements and reflects a saccadic "spike potential." The time course of the iGBR is related to an increase in the rate of saccades following a period of poststimulus saccadic inhibition. Thus, whereas neuronal gamma-band oscillations were shown conclusively with other methods, the broadband transient iGBR recorded by scalp EEG reflects properties of miniature saccade dynamics rather than neuronal oscillations.     

Enantioselective monoterpene alcohol acetylation in Origanum, Mentha and Salvia species

Selected plants within the Origanum, Mentha and Salvia genera, that contain significant amounts of chiral volatile alcohols and their related acetates, exhibit remarkable enantioselectivity of alcohol acetyl transferase (AAT) activity and particularly can discriminate between linalool enantiomers. Origanum dayi AAT produced almost enantiomerically pure (R)-linalyl acetate by enzymatic acetylation of racemic linalool, whereas the closely related O. majorana AAT produced a mixture of (R)- and (S)-linalyl acetate with a ratio of 6:4. V(max) of O. dayi acetylation activity was 30-fold higher for (R)-linalool, whereas in O. majorana no such differences were found.     

The Neural/Immune Gene Ontology: clipping the Gene Ontology for neurological and immunological systems

Background  

The Gene Ontology (GO) is used to describe genes and gene products from many organisms. When used for functional annotation of microarray data, GO is often slimmed by editing so that only higher level terms remain. This practice is designed to improve the summarizing of experimental results by grouping high level terms and the statistical power of GO term enrichment analysis.     

The CCAAT binding factor can mediate interactions between CONSTANS-like proteins and DNA

CONSTANS-Like (COL) proteins are plant-specific nuclear regulators of gene expression but do not contain a known DNA-binding motif. We tested whether a common DNA-binding protein can deliver these proteins to specific cis-acting elements. We screened for proteins that interact with two members of a subgroup of COL proteins. These COL proteins were Tomato COL1 (TCOL1), which does not seem to be involved in the control of flowering time, and the Arabidopsis thaliana CONSTANS (AtCO) protein which mediates photoperiodic induction of flowering. We show that the C-terminal plant-specific CCT (CO, CO-like, TIMING OF CAB EXPRESSION 1) domain of both proteins binds the trimeric CCAAT binding factor (CBF) via its HAP5/NF-YC component. Chromatin immunoprecipitation demonstrated that TCOL is recruited to the CCAAT motifs of the yeast CYC1 and HEM1 promoters by HAP5. In Arabidopsis, each of the three CBF components is encoded by several different genes that are highly transcribed. Under warm long days, high levels of expression of a tomato HAP5 (THAP5a) gene can reduce the flowering time of Arabidopsis. A mutation in the CCT domain of TCOL1 disrupts the interaction with THAP5 and the analogous mutation in AtCO impairs its function and delays flowering. CBFs are therefore likely to recruit COL proteins to their DNA target motifs in planta.     

Electrophysiological Characteristics of Globus Pallidus Neurons

Extracellular recordings in primates have identified two types of neurons in the external segment of the globus pallidus (GPe): high frequency pausers (HFP) and low frequency bursters (LFB). The aim of the current study was to test whether the properties of HFP and LFB neurons recorded extracellularly in the primate GPe are linked to cellular mechanisms underlying the generation of action potential (AP) firing. Thus, we recorded from primate and rat globus pallidus neurons. Extracellular recordings in primates revealed that in addition to differences in firing patterns the APs of neurons in these two groups have different widths (AP_ex). To quantitatively investigate this difference and to explore the heterogeneity of pallidal neurons we carried out cell-attached and whole-cell recordings from acute slices of the rat globus pallidus (GP, the rodent homolog of the primate GPe), examining both spontaneous and evoked activity. Several parameters related to the extracellular activity were extracted in order to subdivide the population of recorded GP neurons into groups. Statistical analysis showed that the GP neurons in the rodents may be differentiated along six cellular parameters into three subgroups. Combining two of these groups allowed a better separation of the population along nine parameters. Four of these parameters (F_max, AP_amp, AP_hw, and AHP_s amplitude) form a subset, suggesting that one group of neurons may generate APs at significantly higher frequencies than the other group. This may suggest that the differences between the HFP and LFB neurons in the primate are related to fundamental underlying differences in their cellular properties.