Low codon bias and high rates of synonymous substitution in Drosophila hydei and D. melanogaster histone genes

We have evaluated codon usage bias in Drosophila histone genes and have obtained the nucleotide sequence of a 5,161-bp D. hydei histone gene repeat unit. This repeat contains genes for all five histone proteins (H1, H2a, H2b, H3, and H4) and differs from the previously reported one by a second EcoRI site. These D. hydei repeats have been aligned to each other and to the 5.0-kb (i.e., long) and 4.8-kb (i.e., short) histone repeat types from D. melanogaster. In each species, base composition at synonymous sites is similar to the average genomic composition and approaches that in the small intergenic spacers of the histone gene repeats. Accumulation of synonymous changes at synonymous sites after the species diverged is quite high. Both of these features are consistent with the relatively low codon usage bias observed in these genes when compared with other Drosophila genes. Thus, the generalization that abundantly expressed genes in Drosophila have high codon bias and low rates of silent substitution does not hold for the histone genes.      

Preparation and characterization of monoclonal antibodies to human adiponectin for its quantitative measurement in serum

Mouse Monoclonal antibodies against human adiponectin were produced by the routine method and the specificity of antibodies was verified. These monoclonal antibodies (MoAbs) interacted with the monomeric and trimeric forms of recombinant adiponectin according to the results of a Western blot analysis. Human blood serum was fractionated by gel filtration, and the protein of these fractions was stained using labeled MoAbs. It was established that a single high-molecular-weight form (HMW) of endogenous adiponectin was detected by this method. The use of competitive enzymelinked immunoassay on the basis of the obtained MoAbs allowed us to show that the sera of healthy male donors contains lower adiponectin concentrations than that of female donors (8.42 ± 1.59 μg/ml vs. 11.01 ± 2.58 μg/ml, p = 0.01). We also detected statistically significant lower adiponectin levels in the serum of patients with coronary artery disease for both men (6.01 ± 2.73 μg/ml vs. 8.42 ± 1.59 μg/ml, p = 0.015) and women (5.79 ± 2.98 μg/ml vs. 11.01 ± 2.58 μg/ml, p = 0.0003). Therefore, the developed methods for the analysis of the HMW form of adiponectin can be helpful in the diagnostics of the possible implications and assessment of unfavorable prognoses in patients with cardiovascular disorders.     

Suicidal process,suicidal communication and psychosocial situation of young suicide attempters in a rural Vietnamese community

The study aimed to explore the suicidal process, suicidal communication and psychosocial situation of young suicide attempters in a rural community in Hanoi, Vietnam. Semi-structured interviews were conducted, in a community setting, with 19 suicide attempters aged 15-24 who had been consecutively hospitalized in an intensive care unit. In 12 of 19 cases, the first pressing, distinct and constant suicidal thoughts appeared less than one day before the suicide attempt in question. However, distress and mild, fleeting suicidal thoughts had been present up to six months before the suicide attempt in 16 cases. Five respondents had a suicide plan one to three days before attempting suicide. Altogether, 13 engaged in some form of suicidal communication before their attempt. This communication was, however, difficult for outsiders to interpret. Twelve of the respondents were victims of regular physical abuse and 16 had suffered psychological violence for at least one year before attempting suicide. Eighteen of the respondents used pesticides or raticides in their suicide attempts. None sought advice or consultation in the community despite long-standing psychosocial problems. The strategy of reducing the availability of suicide means (e.g., pesticides or raticides) in Asian countries should be complemented with a long-term suicide-preventive strategy that targets school dropouts and domestic violence, and promotes coping abilities and communication about psychological and social problems as well as recognition of signs of distress and suicidal communication.     

Proof-of-concept human laboratory study for protracted abstinence in alcohol dependence: effects of gabapentin

There is a need for safe medications that can effectively support recovery by treating symptoms of protracted abstinence that may precipitate relapse in alcoholics, e.g. craving and disturbances in sleep and mood. This proof-of-concept study reports on the effectiveness of gabapentin 1200 mg for attenuating these symptoms in a non-treatment-seeking sample of cue-reactive, alcohol-dependent individuals. Subjects were 33 paid volunteers with current Diagnostic and Statistical Manual of Mental Disorders-IV alcohol dependence and a strength of craving rating 1 SD or greater for alcohol than water cues. Subjects were randomly assigned to gabapentin or placebo for 1 week and then participated in a within-subjects trial where each was exposed to standardized sets of pleasant, neutral and unpleasant visual stimuli followed by alcohol or water cues. Gabapentin was associated with significantly greater reductions than placebo on several measures of subjective craving for alcohol as well as for affectively evoked craving. Gabapentin was also associated with significant improvement on several measures of sleep quality. Side effects were minimal, and gabapentin effects were not found to resemble any major classes of abused drugs. Results suggest that gabapentin may be effective for treating the protracted abstinence phase in alcohol dependence and that a randomized clinical trial would be an appropriate next step. The study also suggests the value of cue-reactivity studies as proof-of-concept screens for potential antirelapse drugs.     

A recently silenced, duplicate PgiC locus in Clarkia

Previous electrophoretic analysis showed that 17 diploid species of the wildflower Clarkia (Onagraceae) have two cytosolic isozymes of phosphoglucose isomerase (PGIC; EC 5.3.1.9), whereas 15 other diploid species have a single PGIC. Molecular studies revealed that the two isozymes in the former species are encoded by duplicate genes, PgiC1 and PgiC2, whereas the single isozyme in the latter is always encoded by PgiC1. Phylogenetic analysis of the nucleotide sequences implied that PgiC2 was silenced four times independently in the genus. Here we describe a psi PgiC2 from C. mildrediae, a species in which only PgiC1 is expressed. The discovery of the psi PgiC2 is significant because it confirms a formal prediction of the phylogenetic analysis. The psi PgiC2 includes 5,039 nucleotides corresponding to 18 of the 23 exons of PgiC, as well as the intervening introns and 3' nontranslated region. The absence of an increase of nucleotide substitutions in its "exons" suggests that the gene was silenced recently. The present study appears to be the first to establish that a specific duplicate gene locus regularly expressed in a group of related plant species has been silenced in one of them. The multiple independent silencings of PgiC2 suggest that it remained functional but inessential in ancestral lineages. We discuss the possibility that PgiC2 may have been preserved in these lineages by selection against mutants causing defective PGIC1- PGIC2 heterodimers.      

Mechanism of functioning of specific sites of interdomain D-E binding of fibrin molecules: interaction of fibrinogen with the N-terminal disulfide node of fibrin

The intermolecular noncovalent binding of complementary fibrin polymerization sites localized in fibrin domains D and E was investigated in the model system. In this system fibrinogen molecules represent the active D domains and the N-terminal disulphide knot of fibrin (N-DSK) represents the active E domain. Quantitative definition of insoluble fibrinogen and N-DSK copolymer and light scattering data of their mixtures before the appearance of visible precipitate show that complexing of these structures decreases with an increase of the temperature and ionic strength. The character of this dependence permits certain conclusions to be made on the functioning mechanism for two types of the D-E binding sites. These conclusions are based on an idea of their different affinity. The interdomain binding is primarily realized by D1-E1 sites which are characterized by a high affinity and work mainly on the basis of electrostatic forces. This binding directs the D2-E2 binding which is characterized by lower affinity and which determines the final degree of fibrinogen and N-DSK complexing. These sites function mainly by the H-binding.     

Effect of peptides--structural analogs of NH2-terminal sites of fibrin alpha- and beta-chains--on specific binding of the NH2-terminal disulfide bond of fibrin with fibrinogen

Peptides Gly-Pro-Arg-Pro and Gly-His-Arg-Pro (fibrin alpha- and beta-chain NH2-terminal analogs, respectively) are studied for their effect on fibrinogen (F) and fibrin NH2-terminal disulphide knot (N-DSK) specific binding. Both peptides are found to inhibit the formation of soluble and insoluble F-N-DSK-complexes through inhibition of the interdomain D-E-binding. Gly-Pro-Arg-Pro is much more potent inhibitor than Gly-His-Arg-Pro. Lowering the insoluble F-N-DSK-copolymer quantity by concentration-dependent way these peptides do not change its composition described by the formula [F(N-DSK)2]n. Invariability of fibrinogen and N-DSK copolymer structure is asserted. In this structure neighbouring fibrinogen molecules are bound by two N-DSK molecules via the D1-E1 and D2-E2 binding sites.     

Clinical effectiveness of carbenicillin in suppurative inflammatory processes of varying localization]

The study on sensitivity of clinical strains of the causative agents of purulent infections to carbenicillin showed that 34.6% of the staphylococcal strains, 48.1% of the E. coli strains and 40.3% of the Proteus strains were sensitive to the antibiotic. The strains of Ps. aeruginosa were characterized by moderate sensitivity to carbenicillin. The MTC for most of the isolates ranged within 25-128 microgram/ml. High therapeutic efficacy of carbenicillin in treatment of cases with purulent inflammatory processes of various localization was shown. Positive results were obtained in 82.5% of the adults and 76.2% of the premature infants treated with carbenicillin. A satisfactory therapeutic effect was observed in the cases with sepsis, diffuse purulent peritonitis and abscessing pneumonia treated with carbenicillin in combination with gentamicin.     

Homologies in Cambrian Onychophora

Marine animals related to Recent onychophorans form a significant component in Cambrian faunas. Twelve characters are analysed for homologies in the seven best known Cambrian onychophorans. New morphological evidence and homology analyses for several characters indicate an anteroposterior reversal of Hallucigenia and Microdictyon . Proposed expansion of the trunk in Microdietyon during compaction is rejected. A jaw is tentatively identified in Onychodictyon . The shape of the annulations and the disposition of the tenth leg pair in Aysheaia are reinterpreted, and the suggestion of two somites to the first appendage pair is rejected. A suggested morphocline may mirror the phylogeny of the group. The taxonomic confusion surrounding the supposed radiolarian family Eoconchariidae is cleared