A model of globin evolution

Putative globins have been identified in 426 bacterial, 32 Archaeal and 67 eukaryote genomes. Among these sequences are the hitherto unsuspected presence of single domain sensor globins within Bacteria, Fungi, and a Euryarchaeote. Bayesian phylogenetic trees suggest that their occurrence in the latter two groups could be the result of lateral gene transfer from Bacteria. Iterated psiblast searches based on groups of globin sequences indicate that bacterial flavohemoglobins are closer to metazoan globins than to the other two lineages, the 2-over-2 globins and the globin-coupled sensors. Since Bacteria is the only kingdom to have all the subgroups of the three globin lineages, we propose a working model of globin evolution based on the assumption that all three lineages originated and evolved only in Bacteria. Although the 2-over-2 globins and the globin-coupled sensors recognize flavohemoglobins, there is little recognition between them. Thus, in the first stage of globin evolution, we favor a flavohemoglobin-like single domain protein as the ancestral globin. The next stage comprised the splitting off to single domain 2-over-2 and sensor-like globins, followed by the covalent addition of C-terminal domains resulting in the chimeric flavohemoglobins and globin-coupled sensors. The last stage encompassed the lateral gene transfers of some members of the three globin lineages to specific groups of Archaea and Eukaryotes.     

A neuroglobin-overexpressing transgenic mouse

Neuroglobin (Ngb) is a recently discovered vertebrate globin expressed primarily in neurons. Ngb expression is induced by hypoxia and ischemia, and Ngb protects neurons from these insults. However, its normal physiological role and the mechanism underlying its neuroprotective action are uncertain. We report production of a transgenic mouse in which Ngb is overexpressed under the control of the chicken beta-actin promoter. This mouse should prove helpful for studying Ngb-mediated effects in vitro and in vivo.     

Increased behavioral and neuronal sensitivity to sex pheromone after brief odor experience in a moth

Plasticity in the response to stimuli related to food and oviposition cues is well documented in insects. However, responses to cues related to reproduction, for example, sex pheromones, are considered to be innate and thus not affected by experience. Here we show that brief preexposure to sex pheromones, without ensuing reward, lowers the threshold for behavioral response and augments the sensitivity in antennal lobe interneurons to pheromone compared with naive male moths. Thus, the sex pheromone system in insects can be modulated by experience. In addition, we show that the behavioral attraction to sex pheromone increases after preexposure in a time-dependent manner: a short-term effect, possibly a form of sensitization, and a long-term effect after more than 24 h. The behavioral long-term effect is paralleled by an increase in sensitivity of interneurons in the primary olfactory center, whereas the peripheral olfactory system does not change its sensitivity. We hypothesize that short-term sensitization to sex pheromone serves as a kind of alert system, whereas the long-term effect improves male performance when reproductively active females are present.     

Evolution and function of B chromosome 45S rDNA sequences in Brachycome dichromosomatica.

The origin and activity of 45S rDNA located on micro B chromosomes of the daisy Brachycome dichromosomatica were analysed. The internal transcribed spacer 2 (ITS2) of the 45S rRNA gene was sequenced for micro B, large B, and A chromosomes of B. dichromosomatica cytodeme A2, and conserved differences were identified between sequences originating from A and both types of B chromosomes. Phylogenetic analysis did not identify a species containing an ITS2 sequence more similar to either of the B chromosome sequences than the B. dichromosomatica A chromosome sequences. Thus, an origin of the B chromosomes from A chromosomes at a time prior to the divergence of the 4 cytodemes of B. dichromosomatica is suggested. The frequent (70%) nucleolar non-association of micro B chromosomes suggests inactivity of micro B 45S rDNA.     

Statistical tools for synthesizing lists of differentially expressed features in related experiments

We propose a novel approach for finding a list of features that are commonly perturbed in two or more experiments, quantifying the evidence of dependence between the experiments by a ratio. We present a Bayesian analysis of this ratio, which leads us to suggest two rules for choosing a cut-off on the ranked list of p values. We evaluate and compare the performance of these statistical tools in a simulation study, and show their usefulness on two real datasets.     

Novel self-epitopes derived from aggrecan, fibrillin, and matrix metalloproteinase-3 drive distinct autoreactive T-cell responses in juvenile idiopathic arthritis and in health

Juvenile idiopathic arthritis (JIA) is a heterogeneous autoimmune disease characterized by chronic joint inflammation. Knowing which antigens drive the autoreactive T-cell response in JIA is crucial for the understanding of disease pathogenesis and additionally may provide targets for antigen-specific immune therapy. In this study, we tested 9 self-peptides derived from joint-related autoantigens for T-cell recognition (T-cell proliferative responses and cytokine production) in 36 JIA patients and 15 healthy controls. Positive T-cell proliferative responses (stimulation index ≥2) to one or more peptides were detected in peripheral blood mononuclear cells (PBMC) of 69% of JIA patients irrespective of major histocompatibility complex (MHC) genotype. The peptides derived from aggrecan, fibrillin, and matrix metalloproteinase (MMP)-3 yielded the highest frequency of T-cell proliferative responses in JIA patients. In both the oligoarticular and polyarticular subtypes of JIA, the aggrecan peptide induced T-cell proliferative responses that were inversely related with disease duration. The fibrillin peptide, to our knowledge, is the first identified autoantigen that is primarily recognized in polyarticular JIA patients. Finally, the epitope derived from MMP-3 elicited immune responses in both subtypes of JIA and in healthy controls. Cytokine production in short-term peptide-specific T-cell lines revealed production of interferon-γ (aggrecan/MMP-3) and interleukin (IL)-17 (aggrecan) and inhibition of IL-10 production (aggrecan). Here, we have identified a triplet of self-epitopes, each with distinct patterns of T-cell recognition in JIA patients. Additional experiments need to be performed to explore their qualities and role in disease pathogenesis in further detail.     

Hitch-hiking between cells on lipoprotein particles

Cell surface proteins containing covalently linked lipids associate with specialized membrane domains. Morphogens like Hedgehog and Wnt use their lipid anchors to bind to lipoprotein particles and employ lipoproteins to travel through tissues. Removal of their lipid anchors or decreasing lipoprotein levels give rise to adverse Hedgehog and Wnt signaling. Some parasites can also transfer their glycosylphosphatidylinositol-anchored surface proteins to host lipoprotein particles. These antigen-loaded lipoproteins spread throughout the circulation, and probably hamper an adequate immune response by killing neutrophils. Together, these findings imply a widespread role for lipoproteins in intercellular transfer of lipid-anchored surface proteins, and may have various physiological consequences. Here, we discuss how lipid-modified proteins may be transferred to and from lipoproteins at the cellular level.