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1.
Biochim Biophys Acta Rev Cancer ; 1876(2): 188597, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34332021

RESUMO

Homologous recombination (HR) is involved in repairing DNA double-strand breaks (DSB), the most harmful for the cell. Regulating HR is essential for maintaining genomic stability. In many forms of cancer, overactivation of HR increases tumor resistance to DNA-damaging treatments. RAD51, HR's core protein, is very often over-expressed in these cancers and plays a critical role in cancer cell development and survival. Targeting RAD51 directly to reduce its activity and its expression is therefore one strategy to sensitize and overcome resistance cancer cells to existing DNA-damaging therapies which remains the limiting factor for the success of targeted therapy. This review describes the structure and biological roles of RAD51, summarizes the different targeted sites of RAD51 and its inhibitory compounds discovered and described in the last decade.


Assuntos
Recombinação Homóloga/genética , Rad51 Recombinase/metabolismo , Humanos
2.
J Evol Biol ; 26(5): 1108-16, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23442070

RESUMO

Local climate is an important source of selection on thermal reaction norms that has been well investigated in cline studies, where populations sampled along altitudinal or latitudinal gradients are compared. Several biotic factors vary with climate, but are rarely integrated as alternative agents of selection to climatic factors. We tested the hypothesis that habitat may select for thermal reaction norms and magnitude of phenotypic plasticity in a drosophila parasitoid, independently of the climate of origin. We sampled populations of Leptopilina boulardi, a Drosophila parasitoid in two different habitats, orchards and forests. Orchards offer laying opportunities over small distances for parasitoids, with a low variability in the number of hosts per patch, while forests offer more dispersed and more variable patches. The sampling was realized in a temperate and a Mediterranean climate. We measured egg load, volume of eggs, longevity and lipid content for parasitoids reared at two temperatures. Reaction norms were opposite for populations from forests and orchards for investment in reproduction, independently of the climate of origin. The maximal investment of resources in reproduction occurred at the lower temperature in orchards and the higher temperature in forests. Host distribution differences between habitats may explain these opposite reaction norms. We also observed a flatter reaction norm for egg load in forests than in orchards. This relative canalization may have been selected in response to the higher variability in laying opportunities observed in forests. Our results demonstrate the potential role of resource distribution in evolution of thermal plasticity.


Assuntos
Adaptação Biológica , Evolução Biológica , Drosophila/parasitologia , Interações Hospedeiro-Parasita , Fenótipo , Vespas/fisiologia , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Animais , Clima , Ecossistema , Feminino , Fertilidade , França , Metabolismo dos Lipídeos , Longevidade , Espanha , Temperatura
3.
J Evol Biol ; 25(1): 54-65, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22023097

RESUMO

In host-symbiont interactions, the genes of both host and symbiont can influence phenotypic traits. In the context of a conflict of interest, fitness-related traits are subjected to opposing selective pressures in the genomes of the partners. In the Drosophila parasitoid Leptopilina boulardi, females usually avoid laying eggs into already parasitized larvae. However, when infected by the virus LbFV, they readily lay additional eggs into parasitized larvae. Inducing superparasitism allows the virus to colonize uninfected parasitoid lineages but is usually maladaptive for the parasitoid. We tested for the presence of resistance genes to this behavioural manipulation in the parasitoid genotype by sampling 30 lines from five populations with contrasting viral prevalence, after infecting them with a reference viral isolate. No geographical differentiation was observed although some genotypes underwent less manipulation than others, and these differences were heritable across generations. The viral titre was not correlated with these differences although fecundity differed between extreme lines.


Assuntos
Comportamento Consumatório , Drosophila/parasitologia , Variação Genética , Vírus de Insetos , Fenótipo , Simbiose/genética , Vespas/virologia , Animais , Feminino , Fertilidade , Genótipo , Interações Hospedeiro-Parasita/genética , Padrões de Herança , Vírus de Insetos/genética , Vírus de Insetos/isolamento & purificação , Masculino , Oviposição/genética , Reação em Cadeia da Polimerase , Seleção Genética , Carga Viral , Vespas/genética , Vespas/fisiologia
4.
Mol Ecol ; 19(14): 2995-3007, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20565576

RESUMO

The densities of conspecific individuals may vary through space, especially at the edge of species range. This variation in density is predicted to influence the diffusion of species-specific horizontally transmitted symbionts. However, to date there is very little data on how parasite prevalence varies around the border of a host species. Using a molecular epidemiology approach, we studied the prevalence of a vertically and horizontally transmitted virus at the edge of the geographic range of its insect host, the Drosophila parasitoid wasp Leptopilina boulardi. L. boulardi is a Mediterranean parasitoid species showing a recent range expansion to the north (in France). The LbFV virus manipulates the behaviour of females, increasing their tendency to lay additional eggs in already parasitized Drosophila larvae (superparasitism). This is beneficial for the virus because it allows the virus to be horizontally transferred during superparasitism. We show that LbFV prevalence is very high in central populations, intermediate in marginal populations and almost absent from newly established peripheral populations of L. boulardi. We failed to detect any influence of temperature and diapause on viral transmission efficiency but we observed a clear relationship between prevalence and parasitoid density, and between parasitoid density and the occurrence of superparasitism, as predicted by our epidemiological model. Viral strains were all efficient at inducing the behavioural manipulation and viral gene sequencing revealed very low sequence variation. We conclude that the prevalence reached by the virus critically depends on density-dependent factors, i.e. superparasitism, underlying the selective pressures acting on the virus to manipulate the behaviour of the parasitoid.


Assuntos
Comportamento Animal , Interações Hospedeiro-Patógeno , Vírus de Insetos/genética , Viroses/transmissão , Vespas/virologia , Animais , DNA Viral/genética , Drosophila/parasitologia , Feminino , França , Oviposição , Prevalência
6.
Appl Environ Microbiol ; 75(7): 1916-21, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19181828

RESUMO

Many arthropods are infected with maternally transmitted microorganisms, leading to the coexistence of several intracellular genomes within the host cells, including their own mitochondria. As these genomes are cotransmitted, their patterns of evolution have been intimately linked, with possible consequences for the diversity and evolution of the host mitochondrial DNA. The evolutionary aspects of the situation have been thoroughly investigated, especially the selective sweep on the mitochondria as a result of Wolbachia invasion, whereas direct interactions between mitochondria and intracellular symbionts within the host cells or body have received little attention. Since endosymbionts exploit host resources but mitochondria supply energy to meet the bioenergetic demands of organisms, an unanswered question concerns the correlation between their densities. Here, we investigated the influence of Wolbachia symbiosis on mitochondrial density in two parasitic wasps of Drosophila species, both of which are naturally infected by three Wolbachia strains, but they differ in their degree of dependency on these bacteria. In Leptopilina heterotoma, all Wolbachia strains are facultative, whereas Asobara tabida requires a strain of Wolbachia for oogenesis to occur. In both species, Wolbachia infections are stable and well regulated, since the density of each strain does not depend on the presence or absence of other strains. Using lines that harbor various Wolbachia infection statuses, we found that mitochondrial density was not affected by the infection regardless of the sex and age of the host, which is strongly reminiscent of the independent regulation of specific Wolbachia strains and suggest that the protagonists coexist independently of each other as the result of a long-term coevolutionary interaction.


Assuntos
Drosophila/genética , Drosophila/microbiologia , Interações Hospedeiro-Parasita , Mitocôndrias/genética , Simbiose , Wolbachia/fisiologia , Animais
7.
Parasitology ; 132(Pt 6): 747-56, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16700960

RESUMO

Parasites often induce behavioural changes in their host. However, it is not necessarily easy to determine whether these changes are representative of an adaptation of the parasite (parasite manipulation), an adaptive response of the host or a side-effect of infection. In a solitary parasitoid of Drosophila larvae (Leptopilina boulardi), viral particles (LbFV) modify the host acceptance behaviour of infected females by increasing their tendency to superparasitize. This behavioural alteration allows for the horizontal transmission of the virus within superparasitized Drosophila larvae. To add support for or against the 'manipulation hypothesis', we investigated whether other behavioural components of the parasitoid are affected by viral infection, and whether other forms of horizontal transmission exist. Neither the ability of females to locate host kairomones nor their daily rhythm of locomotor activity was affected by viral infection. However, infected females showed a lower rate of locomotor activity, suggesting a physiological cost of infection. The searching paths of females were also unaffected. Males from infected and uninfected lines showed the same ability to locate females'sexual pheromones. Moreover, alternative modes of horizontal transmission (through food consumption and/or contact with the same Drosophila larvae) did not lead to viral contamination of the parasitoid. The overall specificity of behavioural alteration and of viral horizontal transmission is consistent with the hypothesis that the virus manipulates the behaviour of the parasitoid.


Assuntos
Comportamento Animal/fisiologia , Drosophila/parasitologia , Himenópteros/fisiologia , Himenópteros/virologia , Vírus de Insetos/fisiologia , Animais , Comportamento de Escolha/fisiologia , Transmissão de Doença Infecciosa/veterinária , Drosophila/virologia , Feminino , Interações Hospedeiro-Parasita , Larva/parasitologia , Larva/virologia , Masculino , Atividade Motora/fisiologia , Óvulo , Atrativos Sexuais/fisiologia , Comportamento Sexual Animal/fisiologia , Fatores de Tempo , Vírion/fisiologia
8.
Parasitology ; 131(Pt 2): 161-8, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16145933

RESUMO

Vertically transmitted symbionts can be maintained in a host population only if they do not reduce host fitness, unless they compensate by manipulation of their host's reproduction or have alternative mode of transmission. In Leptopilina boulardi, a parasitoid of Drosophila larvae, some females are infected by viral particles showing both maternal and horizontal transmission. Horizontal transmission occurs when larvae from infected and uninfected individuals of L. boulardi compete in the same host. This situation is facilitated by the increasing tendency to accept already parasitized hosts that viral infection induces in L. boulardi females. Estimation of the adaptive significance of this behavioural modification requires measuring the effect of viral presence on other parasitoid physiological features. Here, we show that viral infection in females imposes no cost on adult survival, a low cost on developmental rate and tibia length, and leads to a strong reduction of locomotor activity. Surprisingly, infected females show higher egg load which could be accounted for by a redirection of energy allocation to egg production. The high intensity of superparasitism in infected females induced a dramatic decrease in pre-imaginal survival of the parasitoid's offspring, representing a potential indirect cost of infection. Low overall pathogeny induced by viral particles appears to be well suited to both transmission modes, both of them requiring females ability to locate and (super)parasitize hosts.


Assuntos
Vírus de Insetos/fisiologia , Vespas/virologia , Animais , Comportamento Animal , Drosophila/parasitologia , Feminino , Interações Hospedeiro-Parasita , Larva/parasitologia , Masculino , Atividade Motora/fisiologia , Óvulo , Vírion/fisiologia
9.
Diabetes Metab ; 31(2): 189-95, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15959425

RESUMO

OBJECTIVE: To compare compliance in type 2 diabetic patients treated with glimepiride once daily or glibenclamide twice to three times daily. METHODS: Poorly controlled type 2 diabetic patients aged 35-65 years were randomized to glimepiride 1 mg once daily or to glibenclamide 1.25 mg twice daily. During initial titration, doses ranged from 1 to 6 mg once daily (glimepiride) and from 1.25 mg twice daily to 5 mg 3 times daily (glibenclamide) to achieve fasting blood glucose < 126 mg/dL. The final titration phase doses were continued during the maintenance phase. Both treatments were packed in electronic pill-boxes fitted with a microprocessor to record dates and times of each opening. Compliance was assessed in terms of mean daily compliance (MDC) and the ratio of days with adequate compliance (DAC). Glycemic control was assessed in terms of the adjusted mean final HbA1c, and the incidence of hypoglycemia. Patient satisfaction was evaluated using the Diabetes Treatment Satisfaction Questionnaire. RESULTS: Compliance over the whole study was generally good, but the MDC was significantly better with glimepiride (87+/-16%) than with glibenclamide (80+/-17%;P < 0.0001). The ratios of DAC for glimepiride and glibenclamide were 87+/-16% and 67+/-24% respectively (P < 0.0001). The adjusted final HbA1c, and the incidence of hypoglycemia were similar in the two groups. Treatment satisfaction on the DTSQc was greater with glimepiride than with glibenclamide (P = 0.0034). CONCLUSIONS: Patient compliance and treatment satisfaction with once-daily glimepiride were significantly better than with glibenclamide 2 to 3 times daily.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Monitoramento de Medicamentos/métodos , Embalagem de Medicamentos/métodos , Eletrônica Médica , Glibureto/uso terapêutico , Hipoglicemiantes/uso terapêutico , Cooperação do Paciente , Compostos de Sulfonilureia/uso terapêutico , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Feminino , França , Glibureto/administração & dosagem , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/sangue , Hipoglicemia/epidemiologia , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Compostos de Sulfonilureia/administração & dosagem
10.
Genetica ; 120(1-3): 181-94, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15088657

RESUMO

Drosophila species are attacked by a number of parasitoid wasps, which constitute an important factor of population regulation. Since Drosophila melanogaster and Drosophila simulans share common parasitoid species, their ecology and evolution can hardly be understood without considering parasitoids. After a short review of data available on Drosophila-parasitoid interactions involving D. melanogaster and D. simulans as hosts, we report field and laboratory experiments investigating the ecological role of Leptopilina parasitoids in Drosophila communities of southern France. Seasonal survey of species abundance shows that strong interspecific interactions occur at both tropic levels. D. simulans progressively replaces D. melanogaster in southern areas suggesting competitive displacement. Parasitoids are responsible for very high Drosophila mortality (up to 90% in some fruits). Field data emphasize the importance of selective pressure that parasitoids exert on Drosophila communities. The two Leptopilina parasites (L. heterotoma and L boulardi) have different local abundances, which vary in time, and they also compete for hosts. We show that parasitoids can mediate the coexistence of D. melanogaster and D. simulans in the laboratory, and thus may contribute to their puzzling coexistence in the field. Conversely, hosts exert selective pressures on parasitoids, and development on either D. melanogaster or D. simulans strongly affects fitness of adult wasps in a temperature-dependent fashion. Local variation in host species abundance and diversity could thus account for the genetic differentiation we observed in one parasitoid species. Despite laboratory studies cannot fully explain complex field situations, it is clear that the ecology and evolution of Drosophila populations and communities, especially D. melanogaster and D. simulans, are strongly constrained by parasitoids, which should receive more attention.


Assuntos
Drosophila melanogaster/genética , Drosophila melanogaster/parasitologia , Drosophila/genética , Drosophila/parasitologia , Vespas/genética , Animais , Ecologia , França , Genótipo , Interações Hospedeiro-Parasita , Pressão , Especificidade da Espécie , Temperatura
11.
Biofizika ; 47(6): 1073-9, 2002.
Artigo em Russo | MEDLINE | ID: mdl-12500571

RESUMO

Expression of the P-glycoprotein (Pgp) is proved to be one of the main reasons for the development of the multidrug resistance (MDR) phenotype by cancer cells. The effect of Pgp on the properties of lipid monolayers was studied using membrane fractions of sensitive and Pgp over-expressing multidrug resistance cancer cells containing 11, 24 or 32% of Pgp relative to the total content of membrane proteins. The effect of the Pgp membrane concentration on the properties of monolayers prepared from the membrane fractions was analyzed by the Langmuir-Blodgett method. The subphase composition was found to play a critical role in the stability of monolayers at any Pgp concentration. The optimal subphase comprised 10 mM tris-HCl buffer, pH 6.5, which made it possible to create very stable monolayer films with the pressure of collapse of about 30-40 mN/m. Monolayers prepared from membrane fractions of sensitive cells and cells containing the maximum (32%) amount of Pgp were found to be much more stable compared with fractions comprising 11 or 24% of Pgp. The analysis of monolayer compression dynamics revealed three distinct stages: (1) the self-organization of lipid molecules, which is characterized by an abrupt change of surface potential; (2) the compression of Pgp molecules at the constant potential of monolayers; and (3) the compression of lipid molecules, which is characterized by a quasilinear increase of both pressure and surface potential. It was shown that the specific surface areas of monolayers formed from sensitive and Pgp-enriched membranes containing 11 or 24% of Pgp are very similar, whereas the surface area of the monolayer formed from membranes containing 32% of Pgp is nearly 1.5-fold greater. This fact may reflect the effect of the threshold rearrangement of the structure of lipid molecules or cooperative modifications of lipid-Pgp interactions induced by the increase in the Pgp content from 24 to 32%. The effect of verapamil, a well-known Pgp modulator, on the properties of monolayers was studied. It was show that verapamil is able to induce changes of the surface of Pgp-containing monolayers, and these modifications are maximal at the Pgp:verapamil 1:1 molar ratio. The data present the first experimental evidence for the possible intervention of Pgp modulator into the processes of lipid-lipid or lipid-Pgp cooperative interactions within Pgp-enriched membranes.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/química , Lipídeos de Membrana/química , Linhagem Celular , Membrana Celular/química , Humanos , Estresse Mecânico , Propriedades de Superfície , Verapamil/química
12.
Heredity (Edinb) ; 88(5): 361-5, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11986872

RESUMO

Most cases of Wolbachia infection so far documented in haplodiploid Hymenoptera are associated with parthenogenesis induction. Only three examples of Wolbachia-mediated cytoplasmic incompatibility (CI) have been reported, resulting either in haploidisation of fertilised eggs, which develop into viable males, or in their death. To better document this variability, we studied two new Wolbachia-wasp associations involving Drosophila parasitoids. In Trichopria cf. drosophilae, individuals are infected by two different Wolbachia variants, populations are nearly totally infected, and Wolbachia induces incomplete CI resulting in death of the fertilised eggs. On the other hand, Pachycrepoideus dubius harbours only one bacterial variant, populations are polymorphic for infection, and Wolbachia has no detectable effect. These two cases show that the range of variation in Wolbachia's effects in Hymenoptera is as wide as in diploids, extending from complete CI to an undetectable effect. Cases so far studied show some parallel between the strength of incompatibility, the number of Wolbachia variants infecting each wasp, and the natural infection frequency. These empirical data support theoretical models predicting evolution of CI towards lower levels, resulting in the decline and ultimate loss of infection, and place multiple infections as being an important factor in the evolution of host-Wolbachia associations.


Assuntos
Vespas/microbiologia , Wolbachia/fisiologia , Animais , Citoplasma/fisiologia , Drosophila/parasitologia , Feminino , Fertilidade , Masculino , Polimorfismo Genético , Reprodução
13.
Radiol. bras ; 34(6): 323-326, nov.-dez. 2001. ilus, tab
Artigo em Português | LILACS | ID: lil-322617

RESUMO

OBJETIVO: Determinar a freqüência de identificação das estruturas músculo-ligamentares do assoalho pélvico por meio de exames de ressonância magnética e avaliar o índice de concordância entre os observadores. MÉTODO: Estudo prospectivo em 20 voluntárias assintomáticas, idade de 20 a 80 anos (média de 50 anos). Realizados exames de ressonância magnética pélvica (1,5 T) nas seqüências turbo spin-eco ponderadas em T1 e T2 nos planos axial e sagital. Os exames foram avaliados por dois observadores independentes, que procuraram identificar os músculos levantador do ânus (músculos coccígeo, pubococcígeo, iliococcígeo e puborretal), obturador interno e compressor da uretra e os ligamentos pubovesical e pubouretral. Os resultados foram comparados com base na freqüência de identificação das estruturas anatômicas e na concordância entre os observadores (índice kappa - k). RESULTADOS: A freqüência de identificação das estruturas variou de 50 por cento a 100 por cento, sendo pouco inferior para os ligamentos. A concordância interobservador na identificação das estruturas foi a seguinte: músculos levantador do ânus e obturador interno (k=1), pubococcígeo (k=0,62), iliococcígeo (k=0,86), puborretal (k=0,27), coccígeo (k=0) e compressor da uretra (k=1), e ligamentos pubovesical (k=0,50) e pubouretral (k=0,58). CONCLUSÃO: A ressonância magnética de pelve permite identificar as principais estruturas músculo-ligamentares do assoalho pélvico na grande maioria dos indivíduos, com boa concordância interobservador.


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética , Diafragma da Pelve/anatomia & histologia , Reprodutibilidade dos Testes
14.
Diabetes Metab ; 27(5 Pt 1): 563-71, 2001 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11694855

RESUMO

OBJECTIVE: The purpose of DIAMETRE (DIabète et Amarel en Monothérapie. Etude de Titration pour la définition des Répondeurs) was to identify factors predictive of response to glimepiride monotherapy in type 2 diabetic patients in the setting of a prospective multicentre open study. MATERIAL AND METHODS: Patients aged 35-70 years with poorly controlled diabetes [fasting plasma glucose (FPG) > or =1,40 g/l and < 3 g/l at baseline] were treated with glimepiride for 6 months, with dosage titrated from 1-6 mg daily, depending on the monthly FPG measurement. Responders were defined as patients with a) FPG < 7.78 mmol/l (1.40 g/l) and HbA(1c) < 7.5% at endpoint, or b) decrease in FPG > or = 20% and/or HbA1c > or = 10%. Stepwise logistic regression analysis was used to identify factors predictive of response. RESULTS: Of 849 patients evaluable for efficacy, 483 (56.9%) were responders. The response was independently influenced by prior treatment with OADs [OR: 0.399 (0.290-0.549), p=0.0001] and diabetes duration [OR: 0.912 (0.877-0.948), p=0.0001]. Ninety patients (9.2%) experienced 124 episodes of symptomatic hypoglycaemia. Multivariate analysis revealed that a high level of HbA(1c) decreased the risk of symptomatic hypoglycaemia [OR: 0.734 (0.628; 0.858), p=0.0001] whereas a family history of type 2 diabetes doubled this risk [OR: 1.956 (1.246; 3.072), p=0.003]. CONCLUSION: This large-scale study, conducted under conditions approximating to current medical practice, confirms that glimepiride has a favourable risk-benefit ratio in type 2 diabetes mellitus. Diabetes duration and previous treatment with OADs reduced the likelihood of being a responder to treatment.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Adulto , Idoso , Apolipoproteínas/sangue , Glicemia/metabolismo , Pressão Sanguínea , Peso Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Angiopatias Diabéticas/fisiopatologia , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemiantes/efeitos adversos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Análise de Regressão , Segurança , Fumar , Compostos de Sulfonilureia/efeitos adversos
15.
Evolution ; 55(8): 1710-4, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11580031

RESUMO

Wolbachia-induced cytoplasmic incompatibility (CI) can have two consequences in haplodiploid insects: fertilized eggs either die (female mortality, FM) or they develop into haploid males (male development, MD). Origin of this diversity remains poorly understood, but current hypotheses invoke variation in damage suffered by paternal chromosomes in incompatible eggs, thus intermediate CI types should be expected. Here, we show the existence of such a particular CI type. In the parasitoid wasp Leptopilina heterotoma, we compared CI effects in crosses involving lines derived from a single inbred line with various Wolbachia infection statuses (natural tri-infection, mono-infection, or no infection). Tri-infected males induce a FM CI type when crossed with either uninfected or mono-infected females. Crossing mono-infected males with uninfected females results in almost complete CI with both reduced offspring production, indicating partial mortality of fertilized eggs, and increased number of sons, showing haploid male development of others. Mono-infected males thus induce an intermediate Cl type when mated with uninfected females. The first evidence of this expected particular CI type demonstrates that no discontinuity separates MD and FM CI types, which appear to be end points of a phenotypic continuum. Second, different CI types can occur within a given species and even within offspring of a single pair. Third, phenotypic expression of the particular CI type induced by a given Wolbachia variant depends on other bacterial variants that co-infect the same tissues. These results support the idea that haplodiploids should be helpful in clarifying evolutionary pathways of insect-Wolbachia associations.


Assuntos
Vespas/microbiologia , Vespas/fisiologia , Wolbachia/fisiologia , Animais , Sobrevivência Celular , Cruzamentos Genéticos , Citoplasma/fisiologia , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/parasitologia , Embrião não Mamífero/fisiologia , Feminino , Masculino , Óvulo/fisiologia , Razão de Masculinidade , Simbiose
16.
Diabet Med ; 18(10): 828-34, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11678974

RESUMO

AIM: To compare the effect of glimepiride in combination with metformin with monotherapy of each drug on glycaemic control in Type 2 diabetic patients. DESIGN AND METHODS: Randomized, double-blind, double-dummy, parallel-group multicentre study conducted in France. Type 2 diabetic patients aged 35-70 years inadequately controlled by metformin monotherapy 2550 mg daily for at least 4 weeks were randomized to either metformin, glimepiride or metformin and glimepiride. RESULTS: Three hundred and seventy-two patients aged 56 +/- 8 years were treated for 5 months. Combination treatment was significantly more efficient in controlling HbA1c (% change + 0.07 +/- 1.20 for metformin, + 0.27 +/- 1.10 for glimepiride, -0.74 +/- 0.96 for combination treatment, P < 0.001), fasting blood glucose (FBG) (mmol/l change + 0.8 +/- 0.4 for metformin, + 0.7 +/- 3.1 for glimepiride and -1.8 +/- 2.2 for combination treatment, P < 0.001) and post-prandial blood glucose (PPBG) (mmol/l change + 1.1 +/- 5.9 for metformin, + 0.1 +/- 5.1 for glimepiride and -2.6 +/- 3.9 for combination treatment, P < 0.001) than either glimepiride or metformin alone. There was no significant difference between metformin or glimepiride monotherapy with respect to the change in HbA1c or FBG; however, glimepiride was significantly more effective than metformin in reducing PPBG. The incidence of symptomatic hypoglycaemia was higher in the combination group than in either monotherapy group (P = 0.039). CONCLUSIONS: Addition of glimepiride to metformin in Type 2 diabetic patients inadequately controlled by metformin alone resulted in superior glycaemic control compared with glimepiride or metformin monotherapy.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa
17.
Proc Natl Acad Sci U S A ; 98(11): 6247-52, 2001 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-11353833

RESUMO

Wolbachia are bacteria that live in the cells of various invertebrate species to which they cause a wide range of effects on physiology and reproduction. We investigated the effect of Wolbachia infection in the parasitic wasp, Asobara tabida Nees (Hymenoptera, Braconidae). In the 13 populations tested, all individuals proved to be infected by Wolbachia. The removal of Wolbachia by antibiotic treatment had a totally unexpected effect-aposymbiotic female wasps were completely incapable of producing mature oocytes and therefore could not reproduce. In contrast, oogenesis was not affected in treated Asobara citri, a closely related species that does not harbor Wolbachia. No difference between natural symbiotic and cured individuals was found for other adult traits including male fertility, locomotor activity, and size, indicating that the effect on oogenesis is highly specific. We argue that indirect effects of the treatments used in our study (antibiotic toxicity or production of toxic agents) are very unlikely to explain the sterility of females, and we present results showing a direct relationship between oocyte production and Wolbachia density in females. We conclude that Wolbachia is necessary for oogenesis in these A. tabida strains, and this association would seem to be the first example of a transition from facultative to obligatory symbiosis in arthropod-Wolbachia associations.


Assuntos
Oogênese/fisiologia , Vespas/fisiologia , Wolbachia/fisiologia , Animais , Antibacterianos/farmacologia , Relação Dose-Resposta a Droga , Feminino , Lipopolissacarídeos , Masculino , Oócitos , Oogênese/efeitos dos fármacos , Rifampina/farmacologia , Simbiose , Vespas/efeitos dos fármacos , Vespas/microbiologia , Wolbachia/genética
18.
Parasitology ; 121 Pt 5: 493-500, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11128800

RESUMO

Endosymbiotic bacteria of the genus Wolbachia infect a number of invertebrate species in which they induce various alterations in host reproduction, mainly cytoplasmic incompatibility (CI). In contrast to most other maternally transmitted parasites, manipulation of host reproduction makes the spread of Wolbachia possible even if they induce a physiological cost on their hosts. Current studies have shown that fitness consequences of Wolbachia infection could range from positive (mutualist) to negative (parasitic) but, in most cases, Wolbachia do not have strong deleterious effects on host fitness and the status of association remains unclear. Here, we show that in the Drosophila parasitoid wasp Leptopilina heterotoma, Wolbachia infection has a negative impact on several host fitness traits of both sexes. Fecundity, adult survival and locomotor performance are significantly reduced, whereas circadian rhythm, development time and offspring sex-ratio are not affected. Although the cost of bacterial infection can be overcome by effects on host reproduction i.e. cytoplasmic incompatibility, it could influence the spread of the bacterium at the early stages of the invasion process. Clearly, results underline the wide spectrum of phenotypic effects of Wolbachia infection and, to our knowledge, Wolbachia infection of L. heterotoma appears to be one of the most virulent that has ever been observed in insects.


Assuntos
Drosophila melanogaster/parasitologia , Vespas/microbiologia , Vespas/fisiologia , Wolbachia/patogenicidade , Animais , Feminino , Fertilidade/fisiologia , Interações Hospedeiro-Parasita , Processamento de Imagem Assistida por Computador , Masculino , Atividade Motora/fisiologia , Razão de Masculinidade , Gravação de Videoteipe , Vespas/crescimento & desenvolvimento
19.
Evolution ; 54(1): 191-200, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10937195

RESUMO

Until now, only two Wolbachia-mediated cytoplasmic incompatibility (CI) types have been described in haplodiploid species, the first in Nasonia (Insect) and the second in Tetranychus (Acari). They both induce a male-biased sex ratio in the incompatible cross. In Nasonia, CI does not reduce fertility since incompatible eggs develop as haploid males, whereas in Tetranychus CI leads to a partial mortality of incompatible eggs, thus reducing the fertility of females. Here, we study Wolbachia infection in a Drosophila parasitoid, Leptopilina heterotoma (Hymenoptera: Figitidae). A survey of Wolbachia infection shows that all natural populations tested are totally infected. Crosses between infected males and cured females show complete incompatibility: almost no females are produced. Moreover, incompatible eggs die early during their development, unlike Nasonia. This early death allows the parasitized Drosophila larva to achieve its development and to emerge. Thus, uninfected females crossed with infected males have reduced offspring production consisting only of males. Evidence of this CI type in insects demonstrates that the difference in CI types of Nasonia and Tetranychus is not due to specific factors of insects or acari. Using theoretical models, we compare the invasion processes of different strategies of Wolbachia: CI in diploid species, the two CI types in haplodiploid species, and parthenogenesis (the classical effect in haplodiploid species). Models show that CI in haplodiploid species is less efficient than in diploid ones. However, the Leptopilina type is advantageous compared to the Nasonia type. Parthenogenesis may be more or less advantageous, depending on the infection cost and on the proportion of fertilized eggs. Finally, we can propose different processes of Wolbachia strategy evolution in haplodiploid species from Nasonia CI type to Leptopilina CI type or parthenogenesis.


Assuntos
Evolução Biológica , Insetos/genética , Insetos/microbiologia , Wolbachia/patogenicidade , Animais , Sequência de Bases , Citoplasma/genética , Primers do DNA/genética , Diploide , Drosophila/genética , Drosophila/microbiologia , Feminino , Haploidia , Himenópteros/genética , Himenópteros/microbiologia , Masculino , Partenogênese , Filogenia , Reprodução , Wolbachia/genética
20.
Proc Biol Sci ; 267(1447): 1005-10, 2000 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-10874750

RESUMO

Most organisms show self-sustained circadian oscillations or biological clocks which control their daily fluctuations in behavioural and physiological activities. While extensive progress has been made in understanding the molecular mechanisms of biological clocks, there have been few clear demonstrations of the fitness value of endogenous rhythms. This study investigated the adaptive significance of circadian rhythms in a Drosophila parasitoid community. The activity rhythms of three sympatric Drosophila parasitoids are out of phase, the competitively inferior parasitoid species being active earlier than the superior competitor. This temporal segregation appears at least partially determined by endogenous periods of the clock which also vary between species and which correlate the time of activity. This earlier activity of the inferior competitor significantly reduces its intrinsic competitive disadvantage when multiparasitism occurs, thus suggesting that natural selection acting on the phase of the rhythm could substantially deviate the endogenous period from the optimal ca. 24 h period. This study demonstrates that temporal segregation of competing species could be endogenously controlled, which undoubtedly favours their coexistence in nature and also shows how natural selection can act on biological clocks to shape daily activity patterns.


Assuntos
Adaptação Fisiológica/fisiologia , Relógios Biológicos/fisiologia , Ritmo Circadiano/fisiologia , Drosophila melanogaster/parasitologia , Vespas/fisiologia , Animais , Drosophila melanogaster/fisiologia , Feminino
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