RESUMEN
In fruit flies, the male-specific fruitless (fru) gene product FruBM plays a central role in establishing the neural circuitry for male courtship behavior by orchestrating the transcription of genes required for the male-type specification of individual neurons. We herein identify the core promoter recognition factor gene Trf2 as a dominant modifier of fru actions. Trf2 knockdown in the sexually dimorphic mAL neurons leads to the loss of a male-specific neurite and a reduction in male courtship vigor. TRF2 forms a repressor complex with FruBM, strongly enhancing the repressor activity of FruBM at the promoter region of the robo1 gene, whose function is required for inhibiting the male-specific neurite formation. In females that lack FruBM, TRF2 stimulates robo1 transcription. Our results suggest that TRF2 switches its own role from an activator to a repressor of transcription upon binding to FruBM, thereby enabling the ipsilateral neurite formation only in males.
Asunto(s)
Proteínas de Drosophila/fisiología , Drosophila melanogaster/fisiología , Proteínas del Tejido Nervioso/fisiología , Caracteres Sexuales , Conducta Sexual Animal/fisiología , Proteína 2 de Unión a Repeticiones Teloméricas/fisiología , Factores de Transcripción/fisiología , Animales , Cortejo , Femenino , Técnicas de Silenciamiento del Gen , Masculino , Red Nerviosa/fisiología , Proteínas del Tejido Nervioso/genética , Neuritas/fisiología , Regiones Promotoras Genéticas/genética , Receptores Inmunológicos/genética , Proteínas Represoras/fisiología , Transcripción Genética/fisiología , Activación Transcripcional/fisiología , Proteínas RoundaboutRESUMEN
Warfarin, an oral anticoagulant is one of the most widely prescribed drugs in modern medicine. Large inter-individuals variability due to age, gender, diet, concurrent drug interactions and variations in CYP2C9 and VKORC1 genes make the management of warfarin therapy challenging and yet no study has been conducted on the Bangladeshi population. The aim of the study was to identify the role of VKORC1 and CYP2C9 polymorphisms in Bangladeshi population in dose requirement of warfarin. We studied 87 heart valve replacement patients who were prescribed warfarin for minimum of 6 months with a target International normalized ratio of 2.0-3.5. Genotyping of VKORC1rs9923231 (-1639 G>A), CYP2C9*2 and CYP2C9*3 was performed by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism. The frequencies of GG, AG and AA genotypes of VKORC1rs9923231 in the studied population were 87.4%, 8%, and 4.6% respectively whereas the frequencies of the CYP2C9*1/3 and CYP2C9*3/3 were 4.6% and 3.4% respectively. The CYP2C9*2 was not found in the studied population. The results of this study indicate that comparatively higher daily maintenance doses of warfarin were required to achieve the target INR for patients carrying both GG genotype of VKORC1rs9923231 and wild type variant of CYP2C9*3 whereas minimum dose were required for patient having AA genotype of VKORC1rs9923231 and *3/*3 variant of CYP2C9.
Asunto(s)
Citocromo P-450 CYP2C9/genética , Vitamina K Epóxido Reductasas/genética , Warfarina/farmacocinética , Anticoagulantes/farmacocinética , Bangladesh , Frecuencia de los Genes , Genotipo , Humanos , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Alprazolam is used as an anxiolytic drug for generalized anxiety disorder and it has been reported to produce sedation and anterograde amnesia. In the current study, we randomly divided 26 healthy male volunteers into two groups: one group taking alprazolam 0.5 mg and the other taking placebo daily for two weeks. We utilized the Cambridge Neuropsychological Test Automated Battery (CANTAB) software to assess the chronic effect of alprazolam. We selected Paired Associates Learning (PAL) and Delayed Matching to Sample (DMS) tests for memory, Rapid Visual Information Processing (RVP) for attention, and Choice Reaction Time (CRT) for psychomotor performance twice: before starting the treatment and after the completion of the treatment. We found statistically significant impairment of visual memory in one parameter of PAL and three parameters of DMS in alprazolam group. The PAL mean trial to success and total correct matching in 0-second delay, 4-second delay, and all delay situation of DMS were impaired in alprazolam group. RVP total hits after two weeks of alprazolam treatment were improved in alprazolam group. But such differences were not observed in placebo group. In our study, we found that chronic administration of alprazolam affects memory but attentive and psychomotor performance remained unaffected.