RNAslider: a faster engine for consecutive windows folding and its application to the analysis of genomic folding asymmetry

Background  

Scanning large genomes with a sliding window in search of locally stable RNA structures is a well motivated problem in bioinformatics. Given a predefined window size L and an RNA sequence S of size N (L < N), the consecutive windows folding problem is to compute the minimal free energy (MFE) for the folding of each of the L-sized substrings of S. The consecutive windows folding problem can be naively solved in O(NL³) by applying any of the classical cubic-time RNA folding algorithms to each of the N-L windows of size L. Recently an O(NL²) solution for this problem has been described.     

Enhancement of Pig Embryonic Implants in Factor VIII KO Mice: A Novel Role for the Coagulation Cascade in Organ Size Control

Very little is known about the mechanisms that contribute to organ size differences between species. In the present study, we used a mouse model of embryonic pig tissue implantation to define the role of host Factor VIII in controlling the final size attained by the implant. We show here that pig embryonic spleen, pancreas, and liver all grow to an increased size in mice that are deficient in the Factor VIII clotting cascade. Similar results were obtained using the transplantation model after treatment with the low molecular weight heparin derivative Clexane which markedly enhanced transplant size. Likewise, enhanced size was found upon treatment with the direct thrombin inhibitor Dabigatran, suggesting that organ size regulation might be mediated by thrombin, downstream of Factor VIII. Considering that thrombin was shown to mediate various functions unrelated to blood clotting, either directly by cleavage of protease-activated receptors (PARs) or indirectly by cleaving osteopontin (OPN) on stroma cells, the role of PAR1 and PAR4 antagonists as well as treatment with cleaved form of OPN (tcOPN) were tested. While the former was not found to have an impact on overgrowth of embryonic pig spleen implants, marked reduction of size was noted upon treatment with the (tcOPN). Collectively, our surprising set of observations suggests that factors of the coagulation cascade have a novel role in organ size control.     

A conserved mechanism controls translation of Rubisco large subunit in different photosynthetic organisms

We previously proposed a mechanism for control of Rubisco expression and assembly during oxidative stress in Chlamydomonas reinhardtii. The N terminus of the large subunit (LSU) comprises an RNA recognition motif (RRM) that is normally buried in the protein, but becomes exposed under oxidizing conditions when the glutathione pool shifts toward its oxidized form. Thus, de novo translation and assembly of Rubisco LSU stop with similar kinetics and the unpaired small subunit (SSU) is rapidly degraded. Here we show that the structure of the N-terminal domain is highly conserved throughout evolution, despite its relatively low sequence similarity. Furthermore, Rubisco from a broad evolutionary range of photosynthetic organisms binds RNA under oxidizing conditions, with dissociation constant values in the nanomolar range. In line with these observations, oxidative stress indeed causes a translational arrest in land plants as well as in Rhodospirillum rubrum, a purple bacterium that lacks the SSU. We highlight an evolutionary conserved element located within alpha-helix B, which is located in the center of the RRM and is also involved in the intramolecular interactions between two LSU chains. Thus, assembly masks the N terminus of the LSU hiding the RRM. When assembly is interrupted due to structural changes that occur under oxidizing conditions or in the absence of a dedicated chaperone, the N-terminal domain can become exposed, leading to the translational arrest of Rubisco LSU. Taken together, these results support a model by which LSU translation is governed by its dimerization. In the case that regulation of type I and type II Rubisco is conserved, the SSU does not appear to be directly involved in LSU translation.     

The specificity enigma: from mechanics to poems.

Biological specificity is usually described in terms of the lock-and-key metaphor. However, this metaphor is to a certain extent misleading and does not grasp the complexity underlying biological specificity. The failure of the lock-and-key metaphor makes it difficult to understand immune recognition. This is the reason why immune specificity has been described as the "Specificity Enigma." In this article, I point at three important differences between biological specificity and mechanical specificity, and suggest an alternative lens through which immune specificity can be considered.     

Dominance and non-complementation among pink-adenineless mutants of Schizophyllum commune involving two discrete genes

Summary In Schizophyllum commune, adenineless mutations conferring pink color fell into two loosely linked loci, ad-4 and ad-7. The mutations were tested for dominance and complementation in dikaryons, and several of the ad-7 mutations were found to be partly dominant over their wild allele and noncomplementary with mutations of the ad-4 locus. The dominance and at least one case of intergenic noncomplementation were verified by quantitative tests.This research was partly supported by the U.S. Department of Agriculture Grant No. A10-CR-66.     

RGB Plots as a Tool for the Simultaneous Visualization of Multiple Data Layers in a Two Dimensional Space

Visualization of multidimensional data helps in understanding complex systems and environments. We present here a red, green, blue (RGB) visualization method that can serve to display environmental properties. The saturation of each color is used to represent the concentration of a given property. The implementation of that figure is illustrated through visualization of three dissolved inorganic nutrient concentrations along a vertical transect of the Mediterranean, as well as through a vertical time series of three phytoplankton group cell numbers. The RGB figures show well known properties of the water column. In addition, they reveal some lesser-known properties, such as regions in shallow water in which the ratio of phosphorus and silica to nitrogen is high, and a deep eukariotic phytoplankton community. Visualization of such data is usually performed with three separate contour or surface plots, and occasionally two properties are presented as an overlay in a single figure. The RGB figure offers a better way to visualize the interactions among the three separate plots than is commonly available.     

Sine-Gordon Equation in (1+2) and (1+3) dimensions: Existence and Classification of Traveling-Wave Solutions

The (1+1)-dimensional Sine-Gordon equation passes integrability tests commonly applied to nonlinear evolution equations. Its kink solutions (one-dimensional fronts) are obtained by a Hirota algorithm. In higher space-dimensions, the equation does not pass these tests. Although it has been derived over the years for quite a few physical systems that have nothing to do with Special Relativity, the Sine-Gordon equation emerges as a non-linear relativistic wave equation. This opens the way for exploiting the tools of the Theory of Special Relativity. Using no more than the relativistic kinematics of tachyonic momentum vectors, from which the solutions are constructed through the Hirota algorithm, the existence and classification of N-moving-front solutions of the (1+2)- and (1+3)-dimensional equations for all N ≥ 1 are presented. In (1+2) dimensions, each multi-front solution propagates rigidly at one velocity. The solutions are divided into two subsets: Solutions whose velocities are lower than a limiting speed, c = 1, or are greater than or equal to c. To connect with concepts of the Theory of Special Relativity, c will be called “the speed of light.” In (1+3)-dimensions, multi-front solutions are characterized by spatial structure and by velocity composition. The spatial structure is either planar (rotated (1+2)-dimensional solutions), or genuinely three-dimensional – branes. Planar solutions, propagate rigidly at one velocity, which is lower than, equal to, or higher than c. Branes must contain clusters of fronts whose speed exceeds c = 1. Some branes are “hybrids”: different clusters of fronts propagate at different velocities. Some velocities may be lower than c but some must be equal to, or exceed, c. Finally, the speed of light cannot be approached from within the subset of slower-than-light solutions in both (1+2) and (1+3) dimensions.     

Implications of the inability of Listeria monocytogenes EGD-e to grow anaerobically due to a deletion in the class III NrdD ribonucleotide reductase for its use as a model laboratory strain

Listeria monocytogenes is a Gram-positive facultative intracellular bacterium that causes life-threatening diseases in humans. It grows and survives in environments of low oxygen tension and under conditions of strict anaerobiosis. Oxygen-limiting conditions may be an important factor in determining its pathogenicity. L. monocytogenes serovar 1/2a strain EGD-e has been employed intensively to elucidate the mechanisms of intracellular multiplication and virulence. Listeria possesses genes encoding class I aerobic and class III anaerobic ribonucleotide reductases (RNRs). The class III RNR consists of a catalytic subunit NrdD and an activase NrdG. Surprisingly, L. monocytogenes EGD-e, but not other L. monocytogenes strains or other listerial species, is unable to grow under strict anaerobic conditions. Inspection of listerial NrdD amino acid sequences revealed a six-amino acid deletion in the C-terminal portion of the EGD-e protein, next to the essential glycyl radical domain. Nevertheless, L. monocytogenes EGD-e can grow under microaerophilic conditions due to the recruitment of residual class Ia RNR activity. A three-dimensional (3D) model based on the structure of bacteriophage T4 NrdD identified the location of the deletion, which appears in a highly conserved part of the NrdD RNR structure, in the α/β barrel domain near the glycyl radical domain. The deleted KITPFE region is essential either for interactions with the NrdG activase or, indirectly, for the stability of the glycyl radical loop. Given that L. monocytogenes EGD-e lacks a functional anaerobic RNR, the present findings are relevant to the interpretation of studies of pathogenesis with this strain specifically, in particular under conditions of low oxygen tension.     

A novel fast mechanism for GPCR-mediated signal transduction--control of neurotransmitter release

Reliable neuronal communication depends on accurate temporal correlation between the action potential and neurotransmitter release. Although a requirement for Ca(2+) in neurotransmitter release is amply documented, recent studies have shown that voltage-sensitive G protein-coupled receptors (GPCRs) are also involved in this process. However, how slow-acting GPCRs control fast neurotransmitter release is an unsolved question. Here we examine whether the recently discovered fast depolarization-induced charge movement in the M(2)-muscarinic receptor (M(2)R) is responsible for M(2)R-mediated control of acetylcholine release. We show that inhibition of the M(2)R charge movement in Xenopus oocytes correlated well with inhibition of acetylcholine release at the mouse neuromuscular junction. Our results suggest that, in addition to Ca(2+) influx, charge movement in GPCRs is also necessary for release control.