Lipid rafts: bringing order to chaos

Lipid rafts are subdomains of the plasma membrane that contain high concentrations of cholesterol and glycosphingolipids. They exist as distinct liquid-ordered regions of the membrane that are resistant to extraction with nonionic detergents. Rafts appear to be small in size, but may constitute a relatively large fraction of the plasma membrane. While rafts have a distinctive protein and lipid composition, all rafts do not appear to be identical in terms of either the proteins or the lipids that they contain. A variety of proteins, especially those involved in cell signaling, have been shown to partition into lipid rafts. As a result, lipid rafts are thought to be involved in the regulation of signal transduction. Experimental evidence suggests that there are probably several different mechanisms through which rafts control cell signaling. For example, rafts may contain incomplete signaling pathways that are activated when a receptor or other required molecule is recruited into the raft. Rafts may also be important in limiting signaling, either by physical sequestration of signaling components to block nonspecific interactions, or by suppressing the intrinsic activity of signaling proteins present within rafts. This review provides an overview of the physical characteristics of lipid rafts and summarizes studies that have helped to elucidate the role of lipid rafts in signaling via receptor tyrosine kinases and G protein-coupled receptors.     

Invertebrate evolution: bringing order to the molluscan chaos

While the seven classes within the phylum Mollusca are clearly defined morphologically and molecularly, relationships between them have long been contentious. Two recent phylogenomic studies take an important step forward with intriguing implications for their evolution.     

Neural chaos and schizophrenia

Recent data indicate that random-like processes are related to the defects in the organization of semantic memory in schizophrenia which is more disorganized and less definable than those of controls with more semantic links and more bizarre and atypical associations. These aspects of schizophrenic cognition are similar to characteristics of chaotic nonlinear dynamical systems. In this context, the hypothesis tested in this study is that dynamic changes of electrodermal activity (EDA) as a measure of brain and autonomic activity may serve as a characteristic which can be used as an indicator of possible neural chaotic process in schizophrenia. In the present study, bilateral EDA in rest conditions were measured in 40 schizophrenic patients and 40 healthy subjects. Results of nonlinear and statistical analysis indicate left-side significant differences of positive largest Lyapunov exponents in schizophrenia patients compared to the control group. This might be interpreted that the neural activity during rest in schizophrenic patients is significantly more chaotic than in the control group. The relationship was confirmed by surrogate data testing. These data suggest that increased neural chaos in patients with schizophrenia may influence brain processes that can cause random-like disorganization of mental processes.     

Targeting glutamate synapses in schizophrenia

Although early clinical observations implicated dopamine dysfunction in the neuropathology of schizophrenia, accumulating evidence suggests that multiple neurotransmitter pathways are dysregulated. The psychotomimetic actions of NMDA receptor antagonists point to an imbalance of glutamatergic signaling. Encouragingly, numerous preclinical and clinical studies have elucidated several potential targets for increasing NMDA receptor function and equilibrating glutamatergic tone, including the metabotropic glutamate receptors 2, 3 and 5, the muscarinic acetylcholine receptors M(1) and M(4), and the glycine transporter GlyT1. Highly specific allosteric and orthosteric ligands have been developed that modify the activity of these novel target proteins, and in this review we summarize both the glutamatergic mechanisms and the novel compounds that are increasing the promise for a multifaceted pharmacological approach to treat schizophrenia.     

Bringing gene order into bacterial shape

A different arrangement of a cluster of genes involved in division and cell-wall synthesis separates bacilli from other bacteria in a phylogenetic analysis. We conclude that the relationships between these genes are not random and might reflect significant events in the evolution of the coupling between growth and division in bacteria.     

Bringing order to protein disorder through comparative genomics and genetic interactions

Background  

Intrinsically disordered regions are widespread, especially in proteomes of higher eukaryotes. Recently, protein disorder has been associated with a wide variety of cellular processes and has been implicated in several human diseases. Despite its apparent functional importance, the sheer range of different roles played by protein disorder often makes its exact contribution difficult to interpret.     

Genome evolution in bacteria: order beneath chaos

Bacterial genomes have been viewed as collections of genes, with each gene and genome evolving more-or-less independently through the acquisition of mutational changes. This historical view has been overturned by the finding that genomes of even closely-related taxa differ widely in gene content. Yet, genomes are more than ever-shuffling collections of genes. Some genes within a genome are more transient than others, conferring a layer of phenotypic lability over a core of genotypic stability; this core decreases in size as the taxa included become increasingly diverse. In addition, some lineages no longer experience high rates of gene turnover, and gene content alters primarily through slow rates of gene loss. More importantly, the cell and molecular biology of the bacterial cell imposes constraints on chromosome composition, maintaining a stable architecture in the face of gene turnover. As a result, genomes reflect the sum of processes that introduce variability, which is then arbitrated by processes that maintain stability.     

Bringing order to a complex molecular machine: The assembly of the bacterial flagella

The bacterial flagellum is an example of elegance in molecular engineering. Flagella dependent motility is a widespread and evolutionarily ancient trait. Diverse bacterial species have evolved unique structural adaptations enabling them to migrate in their environmental niche. Variability exists in the number, location and configuration of flagella, and reflects unique adaptations of the microorganism. The most detailed analysis of flagellar morphogenesis and structure has focused on Escherichia coli and Salmonella enterica. The appendage assembles sequentially from the inner to the outer-most structures. Additionally the temporal order of gene expression correlates with the assembly order of encoded proteins into the final structure. The bacterial flagellar apparatus includes an essential basal body complex that comprises the export machinery required for assembly of the hook and flagellar filament. A review outlining the current understanding of the protein interactions that make up this remarkable structure will be presented, and the associated temporal genetic regulation will be briefly discussed.     

Understanding aging: revealing order out of chaos

Aging is often described as an extremely complex process affecting all of the vital parameters of an individual. In this article, we review how understanding of aging evolved from the first analyses of population survival to the identification of the molecular mechanisms regulating life span. Abundant evidence implicates mitochondria in aging and we focus on the three main components of the mitochondrial theory of aging: (1) increased reactive oxygen species (ROS) production, (2) mitochondrial DNA (mtDNA) damage accumulation, and (3) progressive respiratory chain dysfunction. Experimental evidence shows a relationship between respiratory chain dysfunction, ROS damage, and aging in most of the model organisms. However, involvement of the mtDNA mutations in the aging process is still debated. We recently created a mutant mouse strain with increased levels of somatic mtDNA mutations causing a progressive respiratory chain deficiency and premature aging. These mice demonstrate the fundamental importance of the accumulation of mtDNA alterations in aging. We present here an integrative model where aging is provoked by a single primary event leading to a variety of effects and secondary causes.     

The role of group I metabotropic glutamate receptors in schizophrenia

Summary. It has been proposed that glutamatergic transmission, in particular NMDA receptor function, might be altered in schizophrenia. This hypothesis is mainly based on the observation that uncompetitive NMDA receptor antagonists, e.g. phencyclidine, evoke psychotic symptoms in healthy subjects, whereas agonists interacting at the glycine site of the NMDA receptor complex, e.g. glycine or D-serine, administered jointly with typical neuroleptics, can alleviate schizophrenic symptoms. The function of NMDA receptors may be modulated by group I mGluRs (mGluR1 and mGluR5), which have also been shown to be altered in schizophrenia. In rodents, mGluR5 antagonists, but not mGluR1 ones, potentiate the locomotor activity and the deficit of prepulse inhibition (PPI) induced by uncompetitive NMDA receptor antagonists. These antagonists (of either type) administered alone are not active in the above tests. Hence, antagonists of mGluR1 and mGluR5 may evoke different effects on the NMDA receptor antagonists-induced behavior and, possibly, on schizophrenic symptoms.