Solution conformation of the Pseudomonas syringae MSU 16H phytotoxic lipodepsipeptide Pseudomycin A determined by computer simulations using distance geometry and molecular dynamics from NMR data

Pseudomycin A is a cyclic lipodepsinonapeptide phytotoxin produced by a strain of the plant pathogenic bacterium Pseudomonas syringae. Like other members of this family of bacterial metabolites, it is characterised by a fatty acylated cyclic peptide with mixed chirality and lactonic closure. Several biological activities of Pseudomycin A are lower than those found for some of its congeners, a difference which might depend on the diverse number and distribution of charged residues in the peptide moiety. Hence, it was of interest to investigate its conformation in solution. After the complete interpretation of the two-dimensional NMR spectra, NOE data were obtained and the structure was determined by computer simulations, applying distance geometry and molecular dynamics procedures. The conformation of the large ring of Pseudomycin A in solution includes three rigid structural regions interrupted by three short flexible regions that act as hinges. The overall three-dimensional structure of the cyclic moiety is similar to that of previously studied bioactive lipodepsinonapeptides produced by other pseudomonads.     

Clozapine reduces rehospitalization among schizophrenia patients

Diabetes mellitus positive for antibodies to glutamate decarboxylase is heterogeneous as far as the degree of impairment of endogenous insulin release, though antibodies to glutamate decarboxylase are the most useful marker for future insulin deficiency. To investigate what determines the prognosis of diabetes mellitus positive for antibodies to glutamate decarboxylase, we measured HLA-DRB1 alleles in three groups: 77 cases of insulin-dependent diabetes mellitus (IDDM), 44 of non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure of oral hypoglycemic therapy, and 22 of NIDDM well controlled by diet and/or sulfonylurea agents. The proportion of susceptible and resistant alleles to IDDM determined the degree of insulin deficiency, and comparison of IDDM to NIDDM well controlled by diet and/or sulfonylurea agents revealed significant differences in DRB1*0405 (P < 0.05; RR = 2.82 and RR = 0.89, respectively) and DRB1*1502 (P < 0.001; RR = 0.02 and RR = 2.19, respectively). This study revealed that HLA-DRB1 alleles contribute to determining the prognosis of Japanese diabetes mellitus positive for antibodies to glutamate decarboxylase.     

Arterial blood pressure response to transient arousals from NREM sleep in nonapneic snorers with sleep fragmentation

STUDY OBJECTIVES: To assess the hemodynamic effects of graded arousals during nonrapid eye movement (NREM) sleep in patients with partial upper airway obstruction during sleep without obstructive sleep apnea/hypopnea, overnight beat-to-beat BP was recorded in six patients. SETTING: At the end of each nonapneic obstructive event, EEG responses were graded as follows: grade 2, grade 1, and grade 0 were defined as increased high-frequency EEG lasting >15 s, 3 to 15 s, and no EEG arousals according to the American Sleep Disorders Association, respectively. MEASUREMENTS AND RESULTS: The following were observed during grade 0, 1, and 2 EEG patterns (mean+/-SD): systolic pressure increased by 7.1+/-1.5, 11.7+/-1.9, and 14.2+/-3.4 (p<0.005), respectively; diastolic pressure increased by 4.6+/-0.6, 6.7+/-1.7, and 9.4+/-3.0 (p<0.005), respectively; heart rate increased by 2.9+/-0.4, 3.9+/-2.2, and 8.6+/-4.6 (p<0.005), respectively. CONCLUSIONS: We conclude that nonapneic-nonhypopneic obstructive events are followed by arterial systemic pressure increases whose magnitude varies with the grade of the arousal.     

Transient complete remission of acute lymphoblastic leukemia in relapse after allogeneic bone marrow transplantation induced by donor leukocyte transfusions

We report the case of a young patient with refractory acute lymphoblastic leukemia relapse, after allogeneic bone marrow transplantation, who was treated by donor leukocyte infusions. We observed potent adoptive immunotherapy which produced a cytologic complete remission and total chimeric state. This was of short duration and the patient died of severe graft-versus-host disease. We present a short summary of the literature concerning acute lymphoblastic leukemia and donor leukocyte infusions.     

Chromosomal and genomic organization of Ty1-copia-like retrotransposon sequences in the genus Avena

Regulation of ligand-mediated signal transduction through transmembrane tyrosine kinase growth factor receptors involves phosphorylation of tyrosine residues in the intracellular domain of the receptor. The insulin-like growth factor-I (IGF-I) receptor contains three tyrosine residues in the carboxy-terminal domain at positions 1250, 1251, and 1316. Of these, only the tyrosine at position 1316 is conserved in the homologous position of the insulin receptor. Mutational analysis was used to study the role of these tyrosines in specific outcomes of IGF-I-mediated signal transduction. Mutations in the human IGF-I receptor were either replacement of tyrosines 1250 and 1251 with phenylalanine and histidine (yyFH), respectively, or replacement of the conserved distal tyrosine (position 1316) with phenylalanine (yCF). The yyFH mutation results in an IGF-I receptor with the amino acids found in the homologous position of the human insulin receptor. Cells overexpressing mutated IGF-I receptors were compared with cells expressing only endogenous IGF-I receptors or overexpressing wild-type IGF-I receptors. The ability of yyFH mutant IGF-I receptors to autophosphorylate the beta-subunit or phosphorylate insulin receptor substrate-1 was not significantly different from wild-type type IGF-I receptors. However, one or both of the proximal tyrosine residues (positions 1250 and 1251) in the carboxy-terminus of the IGF-I receptor are essential for IGF-I-stimulation of mitogenic and tumorigenic pathways. IGF-I-induced mitogenesis, measured as thymidine incorporation and cellular proliferation, was abrogated in cells overexpressing mutant IGF-I receptors with replacement of the proximal double tyrosines (positions 1250 and 1251). Fibroblasts expressing this mutant IGF-I receptor formed fewer tumors than the negative control cells, whereas cells expressing wild-type IGF-I receptors formed large tumors in all recipient mice injected. Conversely, cells expressing mutant IGF-I receptors with only the conserved distal tyrosine (position 1316) replaced had slightly reduced IGF-I-stimulated beta-subunit autophosphorylation, thymidine incorporation, and cellular proliferation when compared with cells expressing wild-type receptors. Phosphorylation of insulin receptor substrate-1 by the yCF mutant receptors was not impaired. Despite the ability of these mutant receptors to stimulate mitogenic growth, fibroblasts expressing this mutant receptor were also incapable of forming tumors in recipient nude mice. The distal tyrosine (position 1316) of the IGF-I receptor is crucial for tumor formation but is not essential for IGF-I stimulated mitogenesis. Thus, the tyrosine moieties in the carboxy-terminus of the IGF-I receptor participate in the signal transduction pathways that affect the mitogenic and tumorigenic potentials of cells expressing mutant IGF-I receptors.     

Self-ignition and combustion of a water-fuel emulsion during its injection into heated air. II. Ignition delay time of M-40 fuel oil

We studied experimentally the influence of the degree of water emulsification ofM-40 mazut heated to the water boiling point on the self-ignition time with its pulsed high-pressure injection into heated air. It is shown that water addition does not change the chemistry of the reaction and heating the water-fuel emulsion leads to the disappearance of differences in the ignition character of the emulsion and the moisture-free fuel. It is confirmed that the features of selfignition are determined mostly by conditions of mixture formation. Indirect evidence is obtained that the dynamic tensile strength of the fluid strongly influences the primary dispersion of the jet during its outflow from the sprayer nozzle.Institute of Theoretical and Applied Mechanics, Novosibirsk 630090. Translated from Fizika Goreniya i Vzryva, Vol. 31, No. 4, pp. 20–25, July–August, 1995.     

Transmit permission control on spread ALOHA packets in LEOsatellite systems

A transmit permission control method for improving the throughput characteristics of a low Earth orbit (LEO) satellite communication system employing spread-slotted ALOHA multiple-access scheme is proposed. Both nonfading and fading satellite links are considered. The basic idea of the proposed scheme is to decrease the level of interference at each satellite and, hence, to increase the probability of packet success, by prohibiting the packet transmission from the users with relatively high propagation loss to their connecting satellites. It is shown that the method has the ability to improve the throughput performance in heavy traffic loads and the peak value of the throughput, significantly. It is also shown that the average delay performance of the system employing the proposed scheme is superior to that of the conventional system at heavy traffic loads     

Transient and dynamic average-value modeling of synchronous machinefed load-commutated converters

A new average-value model of a synchronous machine fed load-commutated converter is set forth in which the stator dynamics are combined with the DC link dynamics. This model is shown to he extremely accurate in predicting system transients and in predicting frequency-domain characteristics such as the impedance looking into the synchronous machine fed load-commutated converter. The model is verified against a detailed computer simulation and against a hardware test system, thus providing a three-way comparison. The proposed model is shown to be much more accurate than models in which the stator dynamics are neglected     

Useful NMR solvent mixture for polyesters: Trifluoroacetic acid-d/chloroform-d

Summary NMR spectra of high molecular weight polyesters such as polyglycolide (PG) and poly(ethylene terephthalate) (PET) have not been available because of low solubility in suitable NMR solvents. Although PG is not soluble enough at ambient temperatures for NMR spectra in either chloroform-d or trifluoroacetic acid-d alone, it dissolves readily to over 0.9% in a mixture of the two. At this concentration, ¹H and ¹³C spectra can be obtained on samples where end group signals are visible from which molecular weights can readily be determined. The solutions are stable up to at least four days when moisture is excluded. NMR spectra of PET can likewise be obtained at ambient temperatures in the solvent mixture which dissolves up to at least 0.6% of PET.