The druggable genome.

An assessment of the number of molecular targets that represent an opportunity for therapeutic intervention is crucial to the development of post-genomic research strategies within the pharmaceutical industry. Now that we know the size of the human genome, it is interesting to consider just how many molecular targets this opportunity represents. We start from the position that we understand the properties that are required for a good drug, and therefore must be able to understand what makes a good drug target.

Consideraciones acerca de lo biológico en la esquizofrenia / Biological factors of schizopherenia

Se enjuicia la endeblez del concepto actual de esquizofrenia y se revisan las ideas acerca del valor de los factores biológicos en su etiología. Se concluye que: 1) En vez de una enfermedad, la esquizofrenia es un síndrome con diversas subformas, unas con influencia genética indudable del modelo de un gen dominante o recesivo o con heterogeneidad y, otras, poligénicas y con riesgo o vulnerabilidad genéticas. 2) Las dos primeras subformas, monogenéticas y heterogenéticas, se vinculan a casos crónicos, con personalidad pre-mórbida anormal, concordancia en los monocigóticos, hallazgos bioquímicos y fisiopatológicos específicos, de los que se siguen mala respuesta a las fenotiazinas y tendencia a las complicaciones del tipo disquinesia tardía irreversible. 3) Las dos últimas subformas, poligénicas y con riesgo o vulnerabilidad genéticas, se relacionan con casos agudos y episódicos, con personalidad pre-mórbida normal, discordancia en los monocigóticos, ausencia de las anormalidades bioquímicas y fisiológicas detectadas en las dos primeras subformas y, consiguientemente, buena respuesta a las fenotiazinas y escasa frecuencia de complicaciones disquinéticas. Dentro de estas dos últimas grandes subformas, hay gran variedad de esquizofrenias, pero en todas ellas es menester el concurso de factores ambientales para la eclosión del cuadro clínico.

[Pleiotropic effect of the mutation of streptomycin resistance in Micromonospora purpurea var. violacea]. / Pleiotropnyi éffekt mutatsii streptomitsino-rezistentnosti u Micromonospora purpurea var. violacea

Variation of different features of populations of streptomycin-sensitive and streptomycin-resistant forms of M. purpurea var. violacea, an organism producing gentamicin was studied. The population of the initial streptomycin-sensitive culture was characterized by high homogeneity with respect to the cultural, morphological and some physiological properties. The variation of the features, such as the colony size, pigment formation, auxotrophic mutations, antibiotic production significantly increased in populations grown on media with streptomycin. Mutants differing from the initial strain by a complex of cultural, morphological and physiological features and in particular the antibiotic production were isolated from populations of the streptomycin-resistant variants.

[Actinomyces streptomycini mutant blocked in streptidine biosynthesis]. / Mutant Actinomyces streptomycini, blokirovannyi po biosintezu streptidina

Mutant 170 not capable of forming streptidine and streptomycin was obtained using chemical mutagenes. This mutant can produce streptomycin only with suplementation of exogenous streptidine. Experiment with labeled C14-streptidine showed its specific incorporation in streptidine moiety of streptomycin molecule.

[Genetic bases for the selection of microorganisms using analogs]. / Geneticheskie osnovy selektsii mikroorganizmov s ispol'zovaniem analogov

The main mechanisms are considered for biosynthesis processes regulation by means of repression and inhibition with final products. On the basis of these mechanisms the state and prospects of the directed alteration of various stages in regulating the synthesis of primary and secondary metabolites, using breeding selection of mutants resistant to analogues are discussed. The main regularities are presented for using analogues of primary metabolites in the breeding strains with overproduction of various biologically active compounds.

[Production of active mutants of a new species of rifamycin producer resistant to specific actinophage]. / Poluchenie aktivnykh mutantov novogo vida produtsenta rifamitsina, ustoichivykh k spetsifichnomu aktinofagu

Selection of a phage-stable strain of a new species of the rifamycin-producing organism was carried out. The phage-stable mutants were selected with respect to the virulent phage 2739 isolated from a lysogenic culture of the rifamycin-producing organism. Spontaneous phage-stable mutants formed at a rate of 0.8 per cent. Most of them belonged to the morphological colony type with a decreased activity level. No shifts in variation with respect to the property of the antibiotic production were noted under the action of phage 2739. 62 per cent of the phage-stable variants isolated from the secondary growth colonies after infection with the phage were lysogenic and liberated phage 2739 to the culture fluid. Induction of mutations with MNNG, UV and gamma(Co30) rays increased the frequency of the phage-stable mutanta by 1.5 times. Active phage-resistant mutants stable to the phage because of its adsorption and liberating no phage 2739 into liquid media during its cultivation were selected.