Pharyngeal cavity and the gills are the target organ for the repellent action of pardaxin in shark

Pardaxin, an active principle of the repellent secretion of the Red Sea flatfish, Pardachirus marmoratus, elicited severe struggling, mouth paralysis, and transient increase in urea leakage from the gills only when administered to the medium bathing the shark's pharyngeal cavity and gills. An apparatus was constructed which prevents a mixing of the outflow from shark's gills with water bathing its surface skin. It is concluded that in sharks the gills and/or the pharyngeal cavity are the target organ for the repellent action of pardaxin.     

Functions of the testicular gland of blenniid fish: Structural and histochemical investigations

Summary We investigated the functions of the testicular glands of blenniid fishes by fine-structural and histochemical methods. These glands function in the differentiation and nutrition of germ cells, in the secretion of sialomucins, in phagocytosis of germ cells, and in lipid storage.     

Very small microspheres are useful for the determination of cardiac output but not organ blood flow in conscious rabbits

Summary Very small microspheres with a diameter of 8–10 m can be used for the measurement of cardiac output, by the reference flow method, in conscious rabbits. However, they were found not to be suitable for the determination of the distribution of cardiac output or blood flow to most organs. These small microspheres offer certain advantages for the measurement of cardiac output; the numbers required to achieve a specified accuracy of measurement are discussed.     

Genetic and molecular approaches to synthesis and action of the yeast killer toxin

Summary The K1 killer toxin ofSaccharomyces cerevisiae is a secreted, virally-coded protein lethal to sensitive yeasts. Killer yeasts are immune to the toxin they produce. This killer system has been extensively examined from genetic and molecular perspectives. Here we review the biology of killer yeasts, and examine the synthesis and action of the protein toxin and the immunity component. We summarise the structure of the toxin precursor gene and its protein products, outline the proteolytic processing of the toxin subunits from the precursor, and their passage through the yeast secretory pathway. We then discuss the mode of action of the toxin, its lectin-like interaction with a cell wall glucan, and its probable role in forming channels in the yeast plasma membrane. In addition we describe models of how a toxin precursor species functions as the immunity component, probably by interfering with channel formation. We conclude with a review of the functional domains of the toxin structural gene as determined by site-directed mutagenesis. This work has identified regions associated with glucan binding, toxin activity, and immunity.     

Ultrastructure and biochemistry of the pineal organ in deep-sea lanternfishes (Myctophidae)

Summary Pineal structural and biochemical adaptations in lanternfishes included: 1) few photoreceptor outer segment discs; 2) conventional synapses between photoreceptors and pineal neurons; and 3) low levels (0–60 pg/pineal) of serotonin compared to those (>1.0 ng/pineal) in the goldfish pineal organ. These findings suggest reduced photosensory and/or neuroendocrine functions in these deep-sea fishes.     

Critical period for induction of congenital hydrocephalus and dysplasia of subcommissural organ by prenatal X-irradiation in rats

Summary A single whole-body X-irradiation of pregnant Wistar rats at a dose of 1.05 Gy at 10.30, 12.30 and 14.30 h respectively, of gestational day 10 resulted in significantly high incidences of hydrocephalic offspring. No hydrocephalic offspring resulted from X-irradiation of pregnant rats with 1.05 Gy at 16.30 h whereas a dose of 1.22 Gy at 16.30 h resulted in a low but statistically significant incidence of hydrocephalus. Neither 1.05 Gy nor 1.22 Gy X-irradiation of pregnant rats at 18.30 h resulted in any hydrocephalic offspring. Dysplasia of the subcommissural organ was noticed in all the hydrocephalic brains histologically examined.     

The enhanced induction of metallothionein by zinc,its half-life in the marine fishPleuronectes platessa,and the influence of stress factors on metallothionein levels

Summary Intraperitoneal injection of zinc raised levels of a hepatic metallothionein-like species. Assuming that this species was metallothionein (MT) then levels were raised from approximately 20 g/g to 300 g/g in 7 days, and levels thereafter remained high for the next 4 weeks. The half-lives of the protein in liver and kidney from starved fish, measured using in vivo incorporation of³⁵S cysteine at 11°C, were approximately 27 days and 32 days respectively. The following agents failed to stimulate synthesis of MT in plaice: stress (due to catching), endotoxin, dexamethasone, cortisol and turpentine.     

Further support for the postsynaptic action of substance P and its blockade with baclofen in neurons of the guinea-pig hypothalamus in vitro

Effects of substance P on neurons of the guinea-pig hypothalamus in vitro and antagonism between substance P and baclofen were investigated. Substance P increased the firing rate of neurons in the medium containing 0 mM Ca2+ and 12 mM Mg2+. The excitatory action of substance P was antagonized by a low dose of baclofen whereas that of acetylcholine was not antagonized even by much higher doses of baclofen.     

Triple arginines in the cytoplasmic tail of endomannosidase are not essential for type II membrane topology and Golgi localization

Endomannosidase is a Golgi-localized endoglycosidase, which provides an alternate glucosidase-independent pathway of glucose trimming. Using a protease protection assay we demonstrated that Golgi-endomannosidase is a type II membrane protein. The first 25 amino acids of this protein, containing the cytoplasmic tail and the transmembrane domain, were sufficient for Golgi retention of fused reporter proteins alpha1-antitrypsin or green fluorescent protein. However, shortening or deletion of the transmembrane domain prevented Golgi localization, while lengthening it partially reduced Golgi retention of the enzyme. Substitution of the highly conserved positively charged amino acids within the cytoplasmic tail had neither an effect on type II topology nor on the inherent Golgi localization of the enzyme. In contrast, cytoplasmic tail-deleted rat endomannosidase possessed an inverted topology resulting in endoplasmic reticulum mislocalization. Thus, proper topology rather than the presence of positively charged amino acids in the cytoplasmic tail is critical for Golgi localization of rat endomannosidase.     

Epithelial supporting cells can differentiate into outer hair cells and Deiters' cells in the cultured organ of Corti

The organ of Corti is a complex structure containing a single row of inner hair cells (IHCs) and three rows of outer hair cells (OHCs), supported respectively by one row of inner phalangeal cells and three rows of Deiters' cells. When fetal rat organ of Corti explants are cultured, supernumerary OHCs and supernumerary Deiters' cells are produced, without any additional cell proliferation. Analysis of semi- and ultrathin sections revealed that supernumerary OHCs are produced at the distal edge of the organ of Corti. Quantitative analysis of cell types present in the organ of Corti demonstrates that when the number of OHCs increases: (i) the total number of cells remains constant; (ii) the number of Deiters' cells increases; (iii) the number of tectal cells decreases and of Hensen's cells decreases. Using specific HC markers, i.e. jagged2 (Jag2) and Math1, we showed that in addition to existing OHCs, supernumerary OHCs, tectal cells and Hensen's cells expressed these markers in embryonic day 19 organ of Corti explants after 5 days in vitro. The results of this study suggest that Hensen's cells retain the capacity to differentiate into either tectal cells, which differentiate into OHCs, or into undertectal cells which differentiate into Deiters' cells. Received 15 May 2002; received after revision 18 July 2002; accepted 7 August 2002 RID="*" ID="*"Corresponding author.     

Double cone mosaic pattern in the retina of larval and adult piranha,Serrasalmus spilopleura

The mosaic pattern of double cones of retinas in larval and adult piranha,Serrasalmus spilopleura, was examined. Samples from two habitats in the same reservoir, characterized by different light conditions, were examined. The same square pattern was found in all sampled retinas indicating that, for this species, there is no apparent relation between the patterns of double cone arrangement and environmental luminosity.     

二进神经网络表达奇偶校验问题的隐元最小数目上界

二进神经网络采用线性分类,是结构简单又易于实现的一类神经网络,在许多应用领域中都有重要研究价值.对于单隐层二进神经网络,目前隐层规模的确定问题仍然没有明确的研究结论.本文在研究隐层规模问题的过程中,提出了布尔空间的最多孤立样本问题.在二进神经网络隐层神经元各自表达一个"与"关系,所有隐层神经元通过输出元形成"或"关系的情况下,证明了实现最多孤立样本问题需2n?1个隐层神经元.更重要的是,指出了n元奇偶校验问题和最多孤立样本结构的等价性.进一步地,通过引入隐层抑制神经元将隐元数目降为n,说明了抑制神经元在二进神经网络中的重要作用.最后,在Hamming球与SP函数的基础上,揭示出抑制神经元和n元奇偶校验问题的逻辑关系,并给出了奇偶校验问题的逻辑式表达.     

ERKs are the point of divergence of PKA and PKC activation by PTHrP in human skin fibroblasts

Parathyroid hormone-related peptide (PTHrP) receptors, coupled to trimeric G proteins, operate in most target cells through at least three different transduction routes: Gαs-mediated stimulation of adenylylcyclase (AC), Gαq-mediated activation of phospholipase Cβ (PLC) and mitogen-activated protein kinase (MAPK) activation. In this study we investigated the relative role of different pathways in human skin fibroblast prolifera-tion. Using chemical inhibitors and activators of signal transduction, we demonstrated that: (i) AC/cAMP and PLC/1,4,5 inositol triphosphate/diacylglycerol second-messenger systems are simultaneously activated following PTHrP binding to its receptors; (ii) the mitogenic response to PTHrP derives from a balance between two counteracting pathways – an activating route mediated by protein kinase C (PKC) and an inhibitory route mediated by protein kinase A (PKA); (iii) PTHrP mitogenic effects are largely dependent on MAPKs, whose activity can be modulate d by both PKA and PKC. Our results indicate that MAPKs are common targets of both transduction routes and, at the same time, their point of divergence in mediating PTHrP dual and opposite mitogenic effects. Received 2 August 2002; received after revision 10 September 2002; accepted 18 October 2002 RID="*" ID="*"Corresponding author.     

A pivotal role for serotonin (5HT) in the regulation of beta adrenoceptors by antidepressants: reversibility of the action of parachlorophenylalanine by 5-hydroxytroptophan

Summary An acute reduction in the synaptic availability of serotonin (5HT) by p-chlorophenlalanine (PCPA) nullifies the decrease in the density of cortical beta adrenoceptors caused by desipramine (DMI) but does not appreciably alter the attenuation of the norepinephrine (NE) sensitive adenylate cyclase. The analysis of competition-binding curves of [³H]-dihydroalprenolol shows that the affinity of the agonist (–)-isoproterenol for cortical beta adrenoceptors is profoundly reduced following PCPA. This reduction in agonist affinity is enhanced by DMI. Resupplying 5HT by by-passing trptophan hydroxylase inhibition, by administering 5-hydroxytryptophan, converts a DMI non-responsive to a DMI responsive beta adrenoceptor population and shifts the markedly decreased agonist affinity towards the affinity values found in control preparations. The results demonstrate the pivotal role of 5HT in the regulation of the density and agonist affinity characteristics of cortical beta adrenoceptors and contribute to the scientific basis of the serotonin-norepinephrine link hypothesis of affective disorders.Acknowledgments. This work was supported by USPHS grant MH-29228 and the Tennessee Department of Mental Health and Mental Retardation. Present address of L. R. Sterank: NOVA Pharmaceutical Corporation, Baltimore (MD 21228, USA).     

Prediction of protein function and pathways in the genome era

The growing number of completely sequenced genomes adds new dimensions to the use of sequence analysis to predict protein function. Compared with the classical knowledge transfer from one protein to a similar sequence (homology-based function prediction), knowledge about the corresponding genes in other genomes (orthology-based function prediction) provides more specific information about the proteins function, while the analysis of the sequence in its genomic context (context-based function prediction) provides information about its functional context. Whereas homology-based methods predict the molecular function of a protein, genomic context methods predict the biological process in which it plays a role. These complementary approaches can be combined to elucidate complete functional networks and biochemical pathways from the genome sequence of an organism. Here we review recent advances in the field of genomic-context based methods of protein function prediction. Techniques are highlighted with examples, including an analysis that combines information from genomic-context with homology to predict a role of the RNase L inhibitor in the maturation of ribosomal RNA.Received 16 October 2003; received after revision 25 November 2003; accepted 26 November 2003