INIBIZIONE DELL' ALDOSO REDUTTASI DA EMIACETALI

L'aldoso reduttasi (alditol:NADP oxidoreductase, EC 1.1.1.21) (AR) è un enzima citosolico monomerico, appartenente alla famiglia delle aldo-cheto reduttasi, in grado di agire su aldeidi sia aromatiche che alifatiche. Esso catalizza la prima tappa (che è anche quella limitante) della via dei polioli, che consiste nella riduzione NADPH-dipendente del glucosio in sorbitolo. La seconda tappa della suddetta via, catalizzata dalla sorbitolo deidrogenasi, converte il sorbitolo in fruttosio, in una reazione NAD+-dipendente. In condizioni fisiologiche, la via dei polioli coinvolge meno del 3% del glucosio totale presente nella cellula, poiché la quasi totalità dello zucchero viene fosforilato dalla esochinasi, che lo convoglia nella via glicolitica. In condizioni di iperglicemia, come nel caso dei soggetti diabetici, una quota di di glucosio diventa substrato dell'aldoso reduttasi e il flusso di glucosio attraverso la via dei polioli può interessare percentuali fino al 30%. del glucosio totale L’aumento di flusso attraverso la via dei polioli è considerato dannoso per una serie di ragioni: la prima riguarda l'accumulo di sorbitolo all'interno della cellula, che causa uno squilibrio osmotico tale da richiamare acqua dall'esterno, con gravi alterazioni del normale equilibrio elettrolitico. La seconda riguarda l’aumento della produzione di fruttosio che , essendo un agente glicante addirittura migliore del glucosio stesso, può indurre fenomeni di glicazione proteica. Infine, l’aumento del consumo di NADPH ad opera dell’AR determina una riduzione delle difese antiossidanti della cellula. Queste alterazioni metaboliche correlate con l’aumentato flusso attraverso la via dei polioli sono considerate responsabili dell’insorgenza delle cosiddette complicanze diabetiche, che includono cataratta, neuropatie, nefropatie e retinopatie. Per questo l’AR è da tempo considerata un bersaglio per l’identificazione di inibitori che possano portare allo sviluppo di farmaci contro le complicanze del diabete. Sebbene il glucosio rappresenti uno dei substrati di AR più rilevanti dal punto di vista fisiopatologico, la reazione di riduzione catalizzata dall’enzima mostra ancora alcuni aspetti non completamente chiariti. Tra questi, l’apparente cooperatività negativa che è stata osservata con questo substrato e che è stata ascritta all’esistenza di più forme enzimatiche. Il lavoro sperimentale riportato in questa tesi ha fatto uso sia di AR ricombinante umana. I risultati ottenuti indicano che le strutture emiacetaliche degli aldosi esercitano un effetto modulatorio sulla riduzione della forma aldeidica libera catalizzata dall’AR e che questo effetto è in grado di dare spiegazione dell’apparente negatività cooperativa osservata per l’enzima

Fitness of experimental populations of drosophila melanogaster

Summary 1. The present study attemps to examine some aspects of the fitness of populations, here defined as the relative success of populations in surviving and reproducing. A distinction was made between short- term and long- term fitness. The aim of the study was to provide some elucidation of the following basic points in the context of population fitness: a. the measurement of short-term fitness. b. the measurement of term fitness. the relation between short- and longterm fitness. d. the relation between the genetic structure of populations and both types of population fitness. 2. A number of experimental populations of Drosophila melanogaster were started from a highly homozygous inbred line. Some populations were kept at 25° C (K), others at a daily fluctuating temperature (V). K and V populations were studied for a period of two years following initiation ("the experimental period"). Another population (a), derived two years earlier from the same inbred line, was also studied. During the experimental period a number of characters were examined at intervals in all populations. 3. The K and V populations showed a considerable and significant improvement in a number of "direct fitness characters" (female fertility, fecundity, egg hatchability, larva-adult survival, longevity and developmental ). Population a showed an increase in fecundity, longevity and developmental speed, 4. Significant changes were also observed in a number of characters less obviously connected with fitness ("indirect fitness characters"), Of these, sex ratio, body weight, sternopleural chaetae number and asymmetry of the sternopleural chaetae decreased. 5. A pronounced increase in the "population fitness characters" of productivity and population size took place in the K and V populations. Population a also increased in productivity. The coefficient of variation of productivity (and also of a number of direct fitness characters) decreased significantly in the course of the experimental period. 6, The performance in a range of "new" environments, taken as a measure Of long-term fitness, increased. 7. Genetic variance, estimated from heritabilitv tests for sternopleural chaetae number, increased. v 8. It is concluded that the combined action of outbreeding, mutation, recombination, and natural selection was highly effective in bringing about progressive changes in population fitness in the experimental period. The observed divergence of the populations in genetic variance and population fitness is disc used. No systematic differences in genetic variance and fitness were found between the K and V type populations as groups. 9. When populations were ranked for the various direct, indirect and population fitness characters a good concordance was found. It is concluded that productivity and population size provide in general good estimates of population fitness as do fertility, fecundity, asymmetry and coefficients of variation of fitness characters. There is good concordance between the performance in various new environments (except for productivity on a reduced amount of food) and between this aspect of long-term fitness and many of the short-term fitness characters. Short- and long-term fitness as determined here are strongly positively correlated. Genetic variability, the only aspect of the genetic structure of the populqtions considered in the present study, was found to be positively correlated with population fitness. 10. It is argued that estimates of short-term fitness based on only one character have a restricted value. A more general fitness measure based on relative performance in a number of environments and on a combination of criteria is advocated. This should permit quantitative comparisons of the relative fitness of populations and, by allowing predictions of relative future success, has the virtue of being testable.

Single cytotype areas in autopolyploid <i>Plantago media</i> L.

The European distribution of diploid and tetraploid cytotypes of Plantago media has been studied on three different scales: Europe as a whole, the Pyrenees and the upper Rio Gallego valley (Central Pyrenees). On a European scale, the tetraploids are widely and more or less continuously distributed; the diploids are restricted and disjunct. In the Pyrenees the distributions are essentially parapatric with diploids occupying the western part and tetraploids the eastern part. The overlap zone in the Rio Gallego valley consists of a mosaic of diploid, tetraploid and mixed populations. The Pyrenean distribution is best explained by colonization by cytotypes from different origins during the late glacial period followed by secondary contact. The limited intermingling of cytotypes is explained by exclusion, probably genetic and possibly also ecological. Reduced fitness of hybrid cytotypes may account for the existence of large areas with a single cytotype (‘single cytotype areas’) in allopolyploid species in general

Allozymes and RAPDs detect little genetic population substructuring in the Caribbean stoplight parrotfish Sparisoma viride

The genetic population structure of the Caribbean stoplight parrotfish Sparisoma viride was analysed by means of allozyme electrophoresis and randomly amplified polymorphic DNA (RAPD) using blood samples from adult fish that were collected on the reefs of 5 islands (3 sites at Bonaire, 1 each at Curaçao, Jamaica, Tobago and Saba). All allozyme loci showed a single very common allele. Allele frequency differences among the locations were mainly found for rare alleles. Genetic distances among the 7 sample sites ranged from less than 0.0001 to 0.012. The fixation index (FST) for the allozyme loci was 0.0188. Pairwise single enzyme locus FST values were small, but some FST values differed significantly from zero. The allozyme analysis detected significant FST values between Curaçao and the other sample sites. The RAPD data indicated high, but slightly restricted, gene flow among 5 geographic areas. Apparently, dispersal among islands is sufficient to maintain near-homogeneous allele frequencies. We conclude that the local S. viride sub-populations are relatively open and there is a high level of migration among them.

Principes de base de la modélisation en transport

info:eu-repo/semantics/publishe