Mitochondrial defects and hearing loss

The techniques of human molecular genetics have been rapidly applied to the study of hearing loss. These studies have implicated more than 60 loci as causes of nonsyndromic hearing loss. Mutations at more than a dozen nuclear genes have been demonstrated to cause hearing loss, and these have been covered in recent reviews. However, a perhaps unexpected feature of the molecular characterization of human hearing loss has been the occurrence of mutations in the mitochondrial DNA (mtDNA). The importance of mitochondrial function in hearing is emphasized by the recent discovery of mutations in a nuclear-encoded mitochondrial protein which results in hearing loss. This article reviews the current status of our knowledge of mtDNA mutations that have been shown to cause hearing loss, and the suggestion of potential molecular, cellular and tissue-specific pathophysiological mechanisms by which dysfunction of mitochondria may lead to a loss of hearing.     

Impact of acidification on phytoplankton and zooplankton communities

Summary Literature concerning the impacts of acidification on the phytoplankton and zooplankton composition has been reviewed. Available data on the species richness and composition of phytoplankton, attached algae and zooplankton of acidifying systems have been summarized. The effects of water acidification on the primary productivity and biomass of zooplankton have been discussed.     

Purine and pyrimidine receptors

Adenosine 5′-triphosphate (ATP), in addition to its intracellular roles, acts as an extracellular signalling molecule via a rich array of receptors, which have been cloned and characterised. P1 receptors are selective for adenosine, a breakdown product of ATP, produced after degradation by ectonucleotidases. Four subtypes have been identified, A₁, A_2A, A_2B and A₃ receptors. P2 receptors are activated by purines and some subtypes also by pyrimidines. P2X receptors are ligand-gated ion channel receptors and seven subunits have been identified, which form both homomultimers and heteromultimers. P2Y receptors are G protein-coupled receptors, and eight subtypes have been cloned and characterised to date. Received 22 November 2006; received after revision 11 January 2007; accepted 27 February 2007     

Purification and study of equine infectious anemia virus antigens, produced in vivo or in cultured cells]

The G and C antigens of equine infectious anemia virus have been produced in vivo and in infected cell culture, then they have been purified. Their physico-chemical properties have been determined, particularly their molecular weight, their sedimentation coefficient, their density and the iso electric point.     

Deoxyribozymes: useful DNA catalysts in vitro and in vivo

Deoxyribozymes (DNA enzymes; DNAzymes) are catalytic DNA sequences. Using the technique of in vitro selection, individual deoxyribozymes have been identified that catalyze RNA cleavage, RNA ligation, and a growing range of other chemical reactions. DNA enzymes have been used in vitro for applications such as biochemical RNA manipulation and analytical assays for metal ions, small organic compounds, oligonucleotides, and proteins. Deoxyribozymes have also been utilized as in vivo therapeutic agents to destroy specific mRNA targets. Although many conceptual and practical challenges remain to be addressed, deoxyribozymes have substantial promise to contribute meaningfully for applications both in vitro and in vivo.     

Primordial chemistry and enzyme evolution in a hot environment

Ever since the publication of Darwin’s Origin of Species, questions have been raised about whether enough time has elapsed for living organisms to have reached their present level of complexity by mutation and natural selection. More recently, it has become apparent that life originated very early in Earth’s history, and there has been controversy as to whether life originated in a hot or cold environment. This review describes evidence that rising temperature accelerates slow reactions disproportionately, and to a much greater extent than has been generally recognized. Thus, the time that would have been required for primordial chemistry to become established would have been abbreviated profoundly at high temperatures. Moreover, if the catalytic effect of a primitive enzyme (like that of modern enzymes) were to reduce a reaction’s heat of activation, then the rate enhancement that it produced would have increased as the surroundings cooled, quite aside from changes arising from mutation (which is itself highly sensitive to temperature). Some nonenzymatic catalysts of slow reactions, including PLP as a catalyst of amino acid decarboxylation, and the Ce^IV ion as a catalyst of phosphate ester hydrolysis, have been shown to meet that criterion. The work reviewed here suggests that elevated temperatures collapsed the time required for early evolution on Earth, furnishing an appropriate setting for exploring the vast range of chemical possibilities and for the rapid evolution of enzymes from primitive catalysts.     

Function and evolution of channels and transporters in photosynthetic membranes

Chloroplasts from land plants and algae originated from an endosymbiotic event, most likely involving an ancestral photoautotrophic prokaryote related to cyanobacteria. Both chloroplasts and cyanobacteria have thylakoid membranes, harboring pigment-protein complexes that perform the light-dependent reactions of oxygenic photosynthesis. The composition, function and regulation of these complexes have thus far been the major topics in thylakoid membrane research. For many decades, we have also accumulated biochemical and electrophysiological evidence for the existence of solute transthylakoid transport activities that affect photosynthesis. However, research dedicated to molecular identification of the responsible proteins has only recently emerged with the explosion of genomic information. Here we review the current knowledge about channels and transporters from the thylakoid membrane of Arabidopsis thaliana and of the cyanobacterium Synechocystis sp. PCC 6803. No homologues of these proteins have been characterized in algae, although similar sequences could be recognized in many of the available sequenced genomes. Based on phylogenetic analyses, we hypothesize a host origin for most of the so far identified Arabidopsis thylakoid channels and transporters. Additionally, the shift from a non-thylakoid to a thylakoid location appears to have occurred at different times for different transport proteins. We propose that closer control of and provision for the thylakoid by products of the host genome has been an ongoing process, rather than a one-step event. Some of the proteins recruited to serve in the thylakoid may have been the result of the increased specialization of its pigment-protein composition and organization in green plants.     

Geopsychology and geopsychopathology: mental processes and disorders associated with geochemical and geophysical factors

Temporal and regional variations in psychological processes have been associated with three geological factors. They are geochemical profiles, geomagnetic variations, and tectonic stresses. In the geochemical domain, copper, aluminum, zinc, and lithium may influence the incidence of thought disorders such as schizophrenia and senile dementia. These common elements are found in many soils and ground water. Geomagnetic variations have been correlated with enhanced anxiety, sleep disturbances, altered moods, and greater incidences of psychiatric admissions. The effects are usually brief but pervasive. Transient and very local epidemics of bizarre and unusual behaviors are sociological phenomena that sometimes precede increases in earthquake activity within a region; they have been hypothesized to be associated with tectonic strain. Many of the contemporary correlations between geological factors and human behavior are also apparent within historical data. The effects of geophysical and geochemical factors upon human behavior are not artifactual, but they are complex and often not detected by the limited scope of most studies.     

Yeast prions and human prion-like proteins: sequence features and prediction methods

Prions are self-propagating infectious protein isoforms. A growing number of prions have been identified in yeast, each resulting from the conversion of soluble proteins into an insoluble amyloid form. These yeast prions have served as a powerful model system for studying the causes and consequences of prion aggregation. Remarkably, a number of human proteins containing prion-like domains, defined as domains with compositional similarity to yeast prion domains, have recently been linked to various human degenerative diseases, including amyotrophic lateral sclerosis. This suggests that the lessons learned from yeast prions may help in understanding these human diseases. In this review, we examine what has been learned about the amino acid sequence basis for prion aggregation in yeast, and how this information has been used to develop methods to predict aggregation propensity. We then discuss how this information is being applied to understand human disease, and the challenges involved in applying yeast prediction methods to higher organisms.     

Carotenoids and carotenogenesis in cyanobacteria: unique ketocarotenoids and carotenoid glycosides

Cyanobacteria grow by photosynthesis, and necessarily contain chlorophyll and carotenoids, whose main functions are light harvesting and photoprotection. In this review, we discuss the carotenoids, carotenogenesis pathways, and characteristics of carotenogenesis enzymes and genes in some cyanobacteria, whose carotenogenesis enzymes have been functionally confirmed. In these cyanobacteria, various carotenoids have been identified, including the unique ketocarotenoids, echinenone and 4-ketomyxol; and the carotenoid glycosides, myxol glycosides and oscillol diglycosides. From these findings, certain carotenogenesis pathways can be proposed. The different compositions of carotenoids among these species might be due to the presence or absence of certain gene(s), or to different enzyme characteristics. For instance, two distinct beta-carotene ketolases, CrtO and CrtW, are properly used in two pathways depending on the species. One beta-carotene hydroxylase, CrtR, has been identified, and its substrate specificities vary across species. At present, functionally confirmed genes have been found in only a few species, and further studies are needed.     

Geopsychology and geopsychopathology: Mental processes and disorders associated with geochemical and geophysical factors

Summary Temporal and regional variations in psychological processes have been associated with three geological factors. They are geochemical profiles, geomagnetic variations, and tectonic stresses. In the geochemical domain, copper, aluminum, zinc, and lithium may influence the incidence of thought disorders such as schizophrenia and senile dementia. These common elements are found in many soils and ground water. Geomagnetic variations have been correlated with enhanced anxiety, sleep disturbances, altered moods, and greater incidences of psychiatric admissions. The effects are usually brief but pervasive. Transient and very local epidemics of bizarre and unusual behaviors are sociological phenomena that sometimes precede increases in earthquake activity within a region; they have been hypothesized to be associated with tectonic strain. Many of the contemporary correlations between geological factors and human behavior are also apparent within historical data. The effects of geophysical and geochemical factors upon human behavior are not artifactual, but they are complex and often not detected by the limited scope of most studies.     

Molecular parasitology: progress towards the development of vaccines for malaria, filariasis, and schistosomiasis

Advances in molecular biology have allowed for the identification of potential vaccine candidates against several parasitic diseases. Antigens from various life stages of Plasmodium and Schistosoma species and filarial worms have been cloned, sequenced and tested as vaccines. Results to date in animal models have been promising. Modest levels of protection against experimental human malaria have been obtained using both sporozoite and blood-stage antigens. However, a greater understanding of the mechanisms which lead to immunity against parasites is required before effective vaccines can be developed.     

APUD characteristics and immunocytochemistry of avian pituitary corticotrophs.

L-DOPA is taken up and decarboxylated by cells in the avian adenohypophysis, which are situated largely in the cephalic lobe. These APUD cells have been shown by sequential formaldehyde-induced and immunofluorescence to be corticotrophs and the relationship between the two procedures has been found to have a reciprocal quality.     

Genetic control and modifications of peroxidase pattern in two species ofNicotiana and their interspecific hybrid

Summary The peroxidase patterns ofNicotiana suaveolens, N. glutinosa and their interspecific hybrid have been studied, and their possible genetic control analyzed. Modifications of the isozymatic pattern along the plant have been observed.Acknowledgments. The authors thank Prof. J.R. Lacadena and Dr M. Pérez de la Vega for their valuable advice.     

Characterization and antithrombotic action of tissue plasminogen activator

Summary An extractive fibrinolytic enzyme has been characterized and found to belong to the class of vascular plasminogen activators. The agent has been found to have an antithrombotic action in the rabbit.Provided by Dr L. Dussourd d'Hinterland, Laboratoires Pierre Fabre, Castres, France. 1000 units have a fibrinolytic activity of about 15 PU urokinase.     

Cholera toxin structure, gene regulation and pathophysiological and immunological aspects

Many notions regarding the function, structure and regulation of cholera toxin expression have remained essentially unaltered in the last 15 years. At the same time, recent findings have generated additional perspectives. For example, the cholera toxin genes are now known to be carried by a non-lytic bacteriophage, a previously unsuspected condition. Understanding of how the expression of cholera toxin genes is controlled by the bacterium at the molecular level has advanced significantly and relationships with cell-density-associated (quorum-sensing) responses have recently been discovered. Regarding the cell intoxication process, the mode of entry and intracellular transport of cholera toxin are becoming clearer. In the immunological field, the strong oral immunogenicity of the non-toxic B subunit of cholera toxin (CTB) has been exploited in the development of a now widely licensed oral cholera vaccine. Additionally, CTB has been shown to induce tolerance against co-administered (linked) foreign antigens in some autoimmune and allergic diseases. Received 25 October 2007; accepted 12 December 2007     

Recombination frequency and DNA content of the distal part of the second chromosome ofDrosophila hydei sturtevant

Summary Four visible markers, including a newly isolated one, have been cytologically mapped on the second chromosome ofDrosophila hydei. Both the frequency of recombination and the amount of DNA between these markers have been determined. From these data the coefficient of exchange has been calculated.     

Molecular parasitology: Progress towards the development of vaccines for malaria,filariasis, and schistosomiasis

Summary Advances in molecular biology have allowed for the identification of potential vaccine candidates against several parasitic diseases. Antigens from various life stages ofPlasmodium andSchistosoma species and filarial worms have been cloned, sequenced and tested as vaccines. Results to date in animal models have been promising. Modest levels of protection against experimental human malaria have been obtained using both sporozoite and blood-stage antigens. However, a greater understanding of the mechanisms which lead to immunity against parasites is required before effective vaccines can be developed.     

Recent results on hydrogen and hydration in biology studied by neutron macromolecular crystallography

Neutron diffraction provides an experimental method of directly locating hydrogen atoms in proteins, a technique complimentary to ultra-high-resolution [1, 2] X-ray diffraction. Three different types of neutron diffractometers for biological macromolecules have been constructed in Japan, France and the United States, and they have been used to determine the crystal structures of proteins up to resolution limits of 1.5-2.5 A. Results relating to hydrogen positions and hydration patterns in proteins have been obtained from these studies. Examples include the geometrical details of hydrogen bonds, H/D exchange in proteins and oligonucleotides, the role of hydrogen atoms in enzymatic activity and thermostability, and the dynamical behavior of hydration structures, all of which have been extracted from these structural results and reviewed. Other techniques, such as the growth of large single crystals, the preparation of fully deuterated proteins, the use of cryogenic techniques, and a data base of hydrogen and hydration in proteins, will be described.