Neuropeptide F: a ubiquitous invertebrate neuromediator?

Using specific antisera, neuropeptide F (NPF)-related peptides have been identified immunocytochemically as widespread and abundant in the nervous systems of all invertebrate taxa examined so far. To date, four NPFs have been isolated and sequenced: from the cestode, Moniezia expansa and the turbellarian, Artioposthia triangulata, and from the molluscs, Helix aspersa and Aplysia californica; a related nonapeptide has been sequenced also from Loligo vulgaris. These peptides all display structural characteristics of the vertebrate NPY superfamily of peptides and appear, therefore, to represent invertebrate members of this superfamily. In this respect, invertebrate NPFs most likely represent the precursors of the vertebrate NPY superfamily. Homologies between the gene structure of human NPY and molluscan NPF (A. californica) support the view that the NPY/NPF gene is of ancient lineage. Although NPF (A. californica) has been found to inhibit the activity of the abdominal ganglia in Aplysia, its widespread expression in this mollusc would suggest multiple functions; the physiological role(s) of NPFs in other invertebrates awaits examination. The abundance and apparent ubiquitous nature of NPF-related peptides establishes them as evolutionarily-ancient molecules that likely serve important physiological functions in invertebrate neurobiology.     

Interactions among co-infecting parasite species: a mechanism maintaining genetic variation in parasites?

Individuals of free-living organisms are often infected simultaneously by a community of parasites. If the co-infecting parasites interact, then this can add significantly to the diversity of host genotypexparasite genotype interactions. However, interactions between parasite species are usually not examined considering potential variation in interactions between different strain combinations of co-infecting parasites. Here, we examined the importance of interactions between strains of fish eye flukes Diplostomum spathaceum and Diplostomum gasterostei on their infectivity in naive fish hosts. We assessed the infection success of strains of both species in single-strain exposures and in co-exposures with a random strain of the other species. Parasite infection success did not consistently increase or decrease in the co-exposure treatment, but depended on the combinations of co-infecting parasite strains. This disrupted the relative infectivity of D. spathaceum strains observed in single-strain exposures. The infection success of D. gasterostei strains was independent of exposure type. These results suggest that interactions among parasite species may be strain specific and potentially promote maintenance of genetic polymorphism in parasite populations.     

Inhibition of neutrophil apoptosis by acrolein: a mechanism of tobacco-related lung disease?

Cigarette smoking is known to contribute to inflammatory diseases of the respiratory tract by promoting recruitment of inflammatory-immune cells such as neutrophils and perhaps by altering neutrophil functional properties. We investigated whether acrolein, a toxic unsaturated aldehyde found in cigarette smoke, could directly affect neutrophil function. Exposure of freshly isolated human neutrophils to acrolein markedly inhibited spontaneous neutrophil apoptosis as indicated by loss of membrane asymmetry and DNA fragmentation and induced increased neutrophil production of the chemokine interleukin-8 (IL-8). Acrolein (1--50 microM) was found to induce marked activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinases (MAPKs), and inhibition of p38 MAPK activation by SB-203580 prevented acrolein-induced IL-8 release. However, inhibition of either ERK or p38 MAPK did not affect acrolein-dependent inhibition of apoptosis. Acrolein exposure prevented the activation of caspase-3, a crucial step in the execution of neutrophil apoptosis, presumably by direct inhibition of the enzyme. Our results indicate that acrolein may contribute to smoke-induced inflammatory processes in the lung by increasing neutrophil recruitment and reducing neutrophil clearance by apoptosis.     

Tyrosine aminotransferase: a transaminase among others?

Tyrosine aminotransferase (L-tyrosine: 2 oxoglutarate aminotransferase; EC 2.6.1.5; TATase) is the first enzyme in the catabolic pathway of tyrosine. The gene of this transaminase is regulated by glucocorticoid hormones as well as via the cAMP pathway. This review gives a brief survey of the structural and physico-chemical properties of this well-known protein. A comparative study of the properties of TATase with other aminotransferases is also included to analyse this molecule for itself, and not only as a marker used in studies on enzymatic induction. Finally, the regulation of the gene expression is presented, in order to underline a few important features of this model.     

Are aneuploidy and chromosome breakage caused by a CINgle mechanism?

Genetic instability is a hallmark of cancer. Most tumors show complex patterns of translocations, amplifications, and deletions, which have occupied scientists for decades. A specific problem arises in carcinomas with a genetic defect termed chromosomal instability; these solid tumors undergo gains and losses of entire chromosomes, as well as segmental defects caused by chromosome breaks. To date, the apparent inconsistency between intact and broken chromosomes has precluded identification of an underlying mechanism. The recent identification of centromeric breaks alongside aneuploidy in cells with spindle defects indicates that a single mechanism could account for all genetic alterations characteristic of chromosomal instability. Since a poorly controlled spindle can cause merotelic attachments, kinetochore distortion, and subsequent chromosome breakage, spindle defects can generate the sticky ends necessary to start a breakage-fusion-bridge cycle. The characteristic breakpoint of spindle-generated damage, adjacent to the centromere, also explains the losses and gains of whole chromosome arms, which are especially prominent in low-grade tumors. The recent data indicate that spindle defects are an early event in tumor formation, and an important initiator of carcinogenesis.     

Regulation of prostaglandin biosynthesis by human ovarian follicular fluid: a mechanism for ovulation?

We have studied the effect of human ovarian follicular fluid on PG production by bovine seminal vesicles in vitro and found that hFF1 contains a factor of high molecular weight (Mr greater than 30,000) which inhibits PG synthase in a dose-dependent manner. Exposure of this substance to protease activity produced a factor of lower molecular weight (Mr less than 1000) which stimulated PG synthase activity. If this is true of ovarian follicles in vivo, it is possible that increased follicular protease activity stimulates PG synthesis at the time of ovulation.     

Synchrony: a neuronal mechanism for attentional selection?

Attentional selection involves brain processes that select and control the flow of information into the mechanisms that underlie perception and consciousness. One theory proposes that the neural activity that represents the stimuli or events to be attended to is selected through modification of its synchrony. Recent experimental evidence supports this theory, by showing that changes in attentional focus increase the synchrony of neural firing in some neuron pairs and decrease it in others.     

RNA modifications by oxidation: A novel disease mechanism?

The past decade has provided exciting insights into a novel class of central (small) RNA molecules intimately involved in gene regulation. Only a small percentage of our DNA is translated into proteins by mRNA, yet 80% or more of the DNA is transcribed into RNA, and this RNA has been found to encompass various classes of novel regulatory RNAs, including, e.g., microRNAs. It is well known that DNA is constantly oxidized and repaired by complex genome maintenance mechanisms. Analogously, RNA also undergoes significant oxidation, and there are now convincing data suggesting that oxidation, and the consequent loss of integrity of RNA, is a mechanism for disease development. Oxidized RNA is found in a large variety of diseases, and interest has been especially devoted to degenerative brain diseases such as Alzheimer disease, in which up to 50-70% of specific mRNA molecules are reported oxidized, whereas other RNA molecules show virtually no oxidation. The iron-storage disease hemochromatosis exhibits the most prominent general increase in RNA oxidation ever observed. Oxidation of RNA primarily leads to strand breaks and to oxidative base modifications. Oxidized mRNA is recognized by the ribosomes, but the oxidation results in ribosomal stalling and dysfunction, followed by decreased levels of functional protein as well as the production of truncated proteins that do not undergo proper folding and may result in protein aggregation within the cell. Ribosomal dysfunction may also signal apoptosis by p53-independent pathways. There are very few reports on interventions that reduce RNA oxidation, one interesting observation being a reduction in RNA oxidation by ingestion of raw olive oil. High urinary excretion of 8-oxo-guanosine, a biomarker for RNA oxidation, is highly predictive of death in newly diagnosed type 2 diabetics; this demonstrates the clinical relevance of RNA oxidation. Taken collectively the available data suggest that RNA oxidation is a contributing factor in several diseases such as diabetes, hemochromatosis, heart failure, and β-cell destruction. The mechanism involves free iron and hydrogen peroxide from mitochondrial dysfunction that together lead to RNA oxidation that in turn gives rise to truncated proteins that may cause aggregation. Thus RNA oxidation may well be an important novel contributing mechanism for several diseases.     

Autophagy in Apicomplexa: a life sustaining death mechanism?

Programmed cell death (PCD) pathways remain understudied in parasitic protozoa in spite of the fact that they provide potential targets for the development of new therapy. The best understood PCD pathway in higher eukaryotes is apoptosis although emerging evidence also points to autophagy as a mediator of death in certain physiological contexts. Bioinformatic analyses coupled with biochemical and cell biological studies suggest that parasitic protozoa possess the capacity for PCD including a primordial form of apoptosis. Recent work in Toxoplasma and emerging data from Plasmodium suggest that autophagy-related processes may serve as an additional death promoting pathway in Apicomplexa. Detailed mechanistic studies into the molecular basis for PCD in parasitic protozoa represent a fertile area for investigation and drug development.     

Mitotic death: a mechanism of survival? A review

Mitotic death is a delayed response of p53 mutant tumours that are resistant to genotoxic damage. Questions surround why this response is so delayed and how its mechanisms serve a survival function. After uncoupling apoptosis from G1 and S phase arrests and adapting these checkpoints, p53 mutated tumour cells arrive at the G2 compartment where decisions regarding survival and death are made. Missed or insufficient DNA repair in G1 and S phases after severe genotoxic damage results in cells arriving in G2 with an accumulation of point mutations and chromosome breaks. Double strand breaks can be repaired by homologous recombination during G2 arrest. However, cells with excessive chromosome lesions either directly bypass the G2/M checkpoint, starting endocycles from G2 arrest, or are subsequently detected by the spindle checkpoint and present with the features of mitotic death. These complex features include apoptosis from metaphase and mitosis restitution, the latter of which can also facilitate transient endocycles, producing endopolyploid cells. The ability of cells to initiate endocycles during G2 arrest and mitosis restitution most likely reflects their similar molecular environments, with down-regulated mitosis promoting factor activity. Resulting endocycling cells have the ability to repair damaged DNA, and although mostly reproductively dead, in some cases give rise to mitotic progeny. We conclude that the features of mitotic death do not simply represent aberrations of dying cells but are indicative of a switch to amitotic modes of cell survival that may provide additional mechanisms of genotoxic resistance.     

Intermediates: ubiquitous species on folding energy landscapes?

Although intermediates have long been recognised as fascinating species that form during the folding of large proteins, the role that intermediates play in the folding of small, single-domain proteins has been widely debated. Recent discoveries using new, sensitive methods of detection and studies combining simulation and experiment have now converged on a common vision for folding, involving intermediates as ubiquitous stepping stones en route to the native state. The results suggest that the folding energy landscapes of even the smallest proteins possess significant ruggedness in which intermediates stabilized by both native and non-native interactions are common features.     

Non-lichenized Antarctic fungi: transient visitors or members of a cryptic ecosystem?

To date over 1 000 non-lichenized fungal species have been recorded by collection or isolation from Antarctica, and additional taxa are now being identified by molecular studies. The number and variety of species recorded so far suggest that the fungi may be the most diverse biota in the Antarctic, and the additional taxa identified by molecular surveys suggest that the true diversity may be far greater than is currently estimated. Fungi occupy many different ecological niches in the Antarctic, and their significance in these niches is only poorly understood. The majority of species described from the region have been identified as members of broadly cosmopolitan groups, but there is some evidence for both endemic strains and populations. This review brings together the current broad systematic and ecological findings for the non-lichenized Antarctic fungi.