Duchenne muscular dystrophy (DMD) is a common and relentlessly progressive muscle disease. Some interventions have been identified that modestly slow progression and prolong survival, but more meaningful therapies are lacking. The goal of this study is to identify new therapeutic pathways for DMD using a zebrafish model of the disease. To accomplish this, we performed a non-biased drug screen in sapje, a zebrafish line with a recessive nonsense mutation in dystrophin. We identified 6 positive hits (out of 640 total drugs tested) by their ability to prevent abnormal birefringence in sapje. Follow-up analyses demonstrated that fluoxetine, a selective serotonin reuptake inhibitor (SSRI), provided the most substantial benefit. Morpholino-based experimentation confirmed that modulation of the serotonin pathway alone can prevent the dystrophic phenotype, and transcriptomic analysis revealed changes in calcium homeostasis as a potential mechanism. In all, we demonstrate that monoamine agonists can prevent disease in a vertebrate model of DMD. Given the safe and widespread use of SSRIs in clinical practice, our study identifies an attractive target pathway for therapy development.
ObjectiveTo evaluate current club drug use and its potential association with the transmission of HIV/STD among Changsha men who have sex with men (MSM).MethodA cross-sectional survey was conducted by using self-administered questionnaires including information regarding socio-demographics, club drug use, high-risk behaviors, and HIV/STD infections. Multiple methods including venue-based, peer referral using “snowball” techniques, and internet advertisements were used to recruit study participants.ResultsOf the 826 participants, 177 (21.4%) reported that they had used club drugs at some time before or during sex in the past six months. MSM with young age, low education level, and seeking partners through the internet or bars were the main population who used drugs. Poppers were the most common drug used among Changsha MSM. The prevalence of HIV, syphilis, and herpes simplex virus-2 were higher among drug users. There were no significant differences in unprotected sexual intercourse and condom use between drug users and non-users. Compared with non-users, risk behaviors such as group sex, multiple sex partners, and sex with foreigners were more frequent among drug users.ConclusionClub drug use is common among Changsha MSM, and is related to unsafe sex activities and HIV/STD infection. It is necessary to build novel targeted HIV prevention strategies to monitor and reduce club drug use among MSM.
Doubled haploid (DH) lines have become widely used in maize (Zea mays L.) breeding. Haploid genome doubling is an important step in developing DH lines. The low rate of spontaneous genome doubling, which causes low haploid male fertility (HMF), seriously limits the largescale application of DH breeding without colchicine treatment. Our objective was to gain new insights into the genetics controlling HMF to improve the rate of HMF in DH breeding procedures. Haploid populations of 20 inbreds and their 31 single crosses derived from Chinese elite maize germplasm were screened for four traits related to HMF: anther emergence rate, pollen production rate, anther emergence score, and pollen production score. Haploid male fertility was compared between single crosses and their parents. Genotype effects were significant (p < 0.01) for all traits among Chinese elite maize lines and their single crosses, and interactions between genotype and environment were also significant (p < 0.05) for anther performance. Heritabilities ranged from 0.68 to 0.91 for these four traits. Haploid male fertility was controlled by additive effects with two or more genes. Anther emergence score proved to be the best trait for describing HMF and is the most practical trait for breeders. We propose that the potential use of HMF in breeding programs could reduce the need for toxic and costly artificial doubling treatments.
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