The therapeutic potential of monoamine oxidase inhibitors

Monoamine oxidase inhibitors were among the first antidepressants to be discovered and have long been used as such. It now seems that many of these agents might have therapeutic value in several common neurodegenerative conditions, independently of their inhibition of monoamine oxidase activity. However, many claims and some counter-claims have been made about the physiological importance of these enzymes and the potential of their inhibitors. We evaluate these arguments in the light of what we know, and still have to learn, of the structure, function and genetics of the monoamine oxidases and the disparate actions of their inhibitors.     

A comparison of 2 methods for determining the hydrophobicity of Streptococcus groups A and B

A simple method for the evaluation of the hydrophobic properties of streptococci, pathogenic for humans, by their adherence to polystyrene and a modified method for measuring their hydrophobic properties by their sorption on hexadecane have been developed. The results obtained in the evaluation of the hydrophobic properties of streptococci by these two methods have been compared and the complete correlation of these results in classifying the cultures as hydrophobic and hydrophilic has been shown. For the first time the differences in the hydrophobic properties of different strains of group B streptococci have been established.     

Inhibition of anion transport in the red blood cell membrane by anionic and non-anionic arginine-specific reagents

Arginine specific reagents are found to be powerful inhibitors of anion exchange in the red blood cell membrane. Some of these inhibitors such as cyclohexandione, phenylglyoxal and 2, 3-butandione are found to produce their inhibition by interacting covalently with band 3. In contrast to the action of these compounds, the inhibition caused by the phenylglyoxal derivative 4-hydroxy-3-nitrophenyl-glyoxal has been found to be completly reversible. In extending the studies on the mode of action of these compounds on sulfate exchange and to get some more information about their binding site, the degree of inhibition caused by different phenylglyoxal derivatives which have a similar core but differ in their substituent groups have been compared. The interaction between the binding sites of these compounds and other anion transport inhibitors have also been studied.     

Critical role of peptidic toxins in the functional and structural analysis of nicotinic acetylcholine receptors

Animal toxins which interact on various receptors and channels have been often used in the studies of the functional roles of these targets. Nicotinic toxins have been purified from snake and cone venoms and are characterized by high affinity and various selectivity of interactions on the different nicotinic receptors subtypes. Since 30 years they have been used as molecular probes to identify, localize and purify these receptors. Furthermore, they have played a crucial role in the better understanding of their functional properties and have been useful in their structural studies. These peptidic toxins could be chemically synthetized or recombinantly expressed and nonnatural residues could be introduced in their sequences in order to delineate their functional interaction sites. The structural modelisation of toxin-nAChR interaction allows us to understand the antagonistic property of these toxins and open the way to the design of engineered ligands with predetermined specificity, useful as pharmacological tools or therapeutic agents in the numerous diseases involving this receptor family.     

Focus on antivirally active sulfated polysaccharides: from structure-activity analysis to clinical evaluation

In recent years, many compounds having potent antiviral activityin cell culture have been detected and some of these compoundsare currently undergoing either preclinical or clinical evaluation.Among these antiviral substances, naturally occurring sulfatedpolysaccharides and those from synthetic origin are noteworthy.Recently, several controversies over the molecular structuresof sulfated polysaccharides, viral glycoproteins, and cell-surfacereceptors have been resolved, and many aspects of their antiviralactivity have been elucidated. It has become clear that theantiviral properties of sulfated polysaccharides are not onlya simple function of their charge density and chain length butalso their detailed structural features. The in vivo efficacyof these compounds mostly corresponds to their ability to inhibitthe attachment of the virion to the host cell surface althoughin some cases virucidal activity plays an additional role. Thisreview summarizes experimental evidence indicating that sulfatedpolysaccharides might become increasingly important in drugdevelopment for the prevention of sexually transmitted diseasesin the near future.     

The glycerophosphoinositols and their cellular functions

Interest in the glycerophosphoinositols has been increasing recently, on the basis of their biological activities. The cellular metabolism of these water-soluble bioactive phosphoinositide metabolites has been clarified, with the identification of the specific enzyme involved in their synthesis, PLA2IVα (phospholipase A2 IVα), and the definition of their phosphodiesterase-based catabolism, and thus inactivation. The functional roles and mechanisms of action of these compounds have been investigated in different cellular contexts. This has led to their definition in the control of various cell functions, such as cell proliferation in the thyroid and actin cytoskeleton organization in fibroblasts and lymphocytes. Roles for the glycerophosphoinositols in immune and inflammatory responses are also being defined. In addition to these physiological functions, the glycerophosphoinositols have potential anti-metastatic activities that should lead to their pharmacological exploitation.     

Role of molecular biology in understanding the formation of congenital cardiomyopathies in humans

New insights into the genetics of congenital heart diseases in human beings have been obtained these past years. The identification of genes for heart defects have led to a new clinical approach of these malformations in children and their families. These progresses have been made by means of positional cloning as well as through the analysis of mouse models. These findings uncovered a new complexity in the development of cardiac defects and led to revise the different classifications for congenital heart defects. Pediatric cardiologists have also improved their efficiency in defining cardiac phenotypes in affected individuals and in pedigrees with recurrent malformations. At the present time, clinical consequences of these findings remain sparse, though in particular cases genetic counselling has been dramatically improved.     

Purification and characterisation of bovine brain protein kinase C isotypes alpha, beta and gamma

Several polyclonal antisera specific for each of the protein kinase C isotypes alpha, beta 1, beta 2 and gamma have been generated and used to monitor the purification and subsequent separation of these polypeptides. A simple protocol has been developed for the efficient co-purification of these isotypes from bovine brain. The separation of the alpha, beta 1, beta 2 and gamma isotypes has been monitored using the antibodies and pools containing pure alpha, beta 1, and gamma forms have been produced. These isotypes have been characterised for activator dependence and substrate specificity. The results indicate that while the isotypes have similar requirements for magnesium, calcium, ATP and phosphatidylserine, they differ in their dependence on phorbol esters and diacylglycerols. The isotypes also differ in their range of substrate specificities. The implications of these results are discussed.     

Comparative organization of nitrogen fixation-specific genes from Azotobacter vinelandii and Klebsiella pneumoniae: DNA sequence of the nifUSV genes.

In the facultative anaerobe Klebsiella pneumoniae 17 nitrogen fixation-specific genes (nif genes) have been identified. Homologs to 12 of these genes have now been isolated from the aerobic diazotroph Azotobacter vinelandii. Comparative studies have indicated that these diverse microorganisms share striking similarities in the genetic organization of their nif genes and in the primary structure of their individual nif gene products. In this study the complete nucleotide sequence of the nifUSV gene clusters from both K. pneumoniae and A. vinelandii were determined. These genes are identically organized on their respective genomes, and the individual genes and their products exhibit a high degree of interspecies sequence homology.     

Ecological characteristics of scale-bearing Chrysophyceae from The Netherlands

In 1979 50 sampling localities in the south-eastern part of The Netherlands have been sampled once, twice or thrice. The scale-bearing Chrysophyceae have been identified and their abundancies have been estimated. Determinations of pH, alkalinity and water temperature have been done, and the relation between the occurrence of the taxa and these environmental factors was studied. Cluster analysis (TWINSPAN) was used to detect groups of co-occurring taxa. The ordination of these taxa (DECORANA) showed that the first principal component was the pH and the second principal component was the water temperature. Although very few environmental data could be used, these results indicate the importance of the pH (and alkalinity) of fresh waters in the occurrence of the scale-bearing Chrysophyceae, whereas their quantitative development is greatly dependent on the water temperature. Experimental data are needed to test this hypothesis.     

A review of the volatile metabolites of fungi found on wood substrates

The holdings of eight collections of fungi have been examined for organisms isolated from wood and/or trees. Further selection of these fungi has been made according to their reported ability to produce volatile, biologically active metabolites. It is emphasized that the isolates in the collections do not necessarily produce such metabolites. The list of fungi fulfilling these conditions is slightly augmented by reports we have found in the literature, where the fungi concerned have not yet been deposited. The biochemistry of these compounds is considered with particular emphasis on their biosynthesis including that by Homo sapiens. The physiological and toxicological activity of these metabolites is reviewed especially with reference to their potential role in the complex symbioses existent in, for example, a tree. The review concludes with a discussion of areas of botany deserving increased attention in the hope that this will stimulate further work. The statements in the review are based on 173 references.     

Applications of biofeedback to the treatment of asthma: A critical review

Both muscular and respiratory biofeedback procedures have been employed in attempts to reduce symptoms of bronchial asthma. Research relating to these approaches is reviewed in the present article. Biofeedback training both for facial muscle relaxation and for respiratory resistance decrease improves short-term pulmonary function in asthmatic individuals. These forms of training represent promising avenues for the management of asthma. However, unqualified endorsement of these procedures is premature, at the present time, since their influence on asthma-related variables other than pulmonary function has not been determined and since their long-term effects have not been investigated.     

The alphaviruses: gene expression, replication, and evolution.

The alphaviruses are a genus of 26 enveloped viruses that cause disease in humans and domestic animals. Mosquitoes or other hematophagous arthropods serve as vectors for these viruses. The complete sequences of the +/- 11.7-kb plus-strand RNA genomes of eight alphaviruses have been determined, and partial sequences are known for several others; this has made possible evolutionary comparisons between different alphaviruses as well as comparisons of this group of viruses with other animal and plant viruses. Full-length cDNA clones from which infectious RNA can be recovered have been constructed for four alphaviruses; these clones have facilitated many molecular genetic studies as well as the development of these viruses as expression vectors. From these and studies involving biochemical approaches, many details of the replication cycle of the alphaviruses are known. The interactions of the viruses with host cells and host organisms have been exclusively studied, and the molecular basis of virulence and recovery from viral infection have been addressed in a large number of recent papers. The structure of the viruses has been determined to about 2.5 nm, making them the best-characterized enveloped virus to date. Because of the wealth of data that has appeared, these viruses represent a well-characterized system that tell us much about the evolution of RNA viruses, their replication, and their interactions with their hosts. This review summarizes our current knowledge of this group of viruses.     

Applications of biofeedback to the treatment of asthma: a critical review

Both muscular and respiratory biofeedback procedures have been employed in attempts to reduce symptoms of bronchial asthma. Research relating to these approaches is reviewed in the present article. Biofeedback training both for facial muscle relaxation and for respiratory resistance decrease improves short-term pulmonary function in asthmatic individuals. These forms of training represent promising avenues for the management of asthma. However, unqualified endorsement of these procedures is premature, at the present time, since their influence on asthma-related variables other than pulmonary function has not been determined and since their long-term effects have not been investigated.     

Genome evolution in filamentous plant pathogens: why bigger can be better

Many species of fungi and oomycetes are plant pathogens of great economic importance. Over the past 7 years, the genomes of more than 30 of these filamentous plant pathogens have been sequenced, revealing remarkable diversity in genome size and architecture. Whereas the genomes of many parasites and bacterial symbionts have been reduced over time, the genomes of several lineages of filamentous plant pathogens have been shaped by repeat-driven expansions. In these lineages, the genes encoding proteins involved in host interactions are frequently polymorphic and reside within repeat-rich regions of the genome. Here, we review the properties of these adaptable genome regions and the mechanisms underlying their plasticity, and we illustrate cases in which genome plasticity has contributed to the emergence of new virulence traits. We also discuss how genome expansions may have had an impact on the co-evolutionary conflict between these filamentous plant pathogens and their hosts.     

Intracellular functions of galectins

Many galectin family members are detected primarily intracellularly in most of the systems studied, although certain members can be found both inside and outside of cells. Specific functions that are consistent with their intracellular localization have now been documented for some of the galectins. Galectin-1 and -3 have been identified as redundant pre-mRNA splicing factors. Galectin-3, -7, and -12 have been shown to regulate cell growth and apoptosis, being either anti-apoptotic or pro-apoptotic. Galectin-3 and -12 have been shown to regulate the cell cycle. In some cases, the mechanisms by which galectins exert their functions have been partially delineated in relation to known intracellular pathways associated with these processes. In addition, a number of intracellular proteins involved in these processes have been identified as the interacting ligands of certain galectins. This review summarizes the intracellular activities displayed by several galectins and discusses the possible underlying mechanisms.     

Bio-informatic trends for the determination of miRNA-target interactions in mammals

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate mRNAs through a sequence-specific mechanism. By virtue of their structure and mechanism of action, computational methods have been devised to investigate the encoding of miRNA genes and the targets of miRNA action. A variety of assumptions have predicated the implementation of these various computational solutions. Evolutionary sequence conservation, secondary structure, and folding energetics are some of the assumptions that have been used. The success of these different computational solutions has been evaluated for both elucidation of new miRNAs and deducing targets of miRNA action. While the focus is on search techniques for new miRNAs, we have compared the programs miRseeker, miRScan, PalGrade, ProMiR, and miRAlign as examples of implementation of these techniques. For these programs, a benchmark comparison between theoretical estimation and actual identification is possible. We have also compared the target prediction programs TargetScanS, PicTar, DIANA-microT, miRanda, and RNAhybrid. However, it is difficult to rigorously assess the benchmark performance of these programs due to the difficulty in confirming their theoretical predictions.     

Identifying neuropeptide and protein hormone receptors in Drosophila melanogaster by exploiting genomic data.

Most neuropeptide and protein hormone receptors belong to the large superfamily of G-protein-coupled receptors (GPCRs). These cell membrane proteins steer many important processes such as development, reproduction, homeostasis and behaviour when activated by their corresponding ligands. The first insect genome, that of the fruitfly Drosophila melanogaster, was sequenced in 2000, and about 200 GPCRs have been annnotated in this model insect. About 50 of these receptors were predicted to have neuropeptides or protein hormones as their ligands. Since 2000, the cDNAs of most of these candidate receptors have been cloned and for many receptors the endogenous ligand has been identified. In this review, we will give an update about the current knowledge of all Drosophila neuropeptide and protein hormone receptors, and discuss their phylogenetic relationships.     

The diffuse neuroendocrine system. Studies of this newly discovered controlling system in health and disease

Numerous peptides (neuropeptides) have been recently found to be present in both the nervous and endocrine systems composing what is now known as the diffuse neuroendocrine system. Two immunological methods, radioimmunoassay and immunocytochemistry, have been used here in combination to study their distribution and cellular localization. A number of these neuropeptides have recently been found to be abnormal in disease state, thus providing further information as to their role in normal and pathological conditions.