排序方式: 共有21条查询结果,搜索用时 15 毫秒
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Vivet-Boudou V Isel C Sleiman M Smyth R Ben Gaied N Barhoum P Laumond G Bec G Götte M Mak J Aubertin AM Burger A Marquet R 《PloS one》2011,6(11):e27456
The occurrence of resistant viruses to any of the anti-HIV-1 compounds used in the current therapies against AIDS underlies the urge for the development of new drug targets and/or new drugs acting through novel mechanisms. While all anti-HIV-1 nucleoside analogues in clinical use and in clinical trials rely on ribose modifications for activity, we designed nucleosides with a natural deoxyribose moiety and modifications of position 8 of the adenine base. Such modifications might induce a steric clash with helix αH in the thumb domain of the p66 subunit of HIV-1 RT at a distance from the catalytic site, causing delayed chain termination. Eleven new 2'-deoxyadenosine analogues modified on position 8 of the purine base were synthesized and tested in vitro and in cell-based assays. In this paper we demonstrate for the first time that chemical modifications on position 8 of 2'-deoxyadenosine induce delayed chain termination in vitro, and also inhibit DNA synthesis when incorporated in a DNA template strand. Furthermore, one of them had moderate anti-HIV-1 activity in cell-culture. Our results constitute a proof of concept indicating that modification on the base moiety of nucleosides can induce delayed polymerization arrest and inhibit HIV-1 replication. 相似文献
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Nouha Ben-Othman Andhira Vieira Monica Courtney Fabien Record Elisabet Gjernes Fabio Avolio Biljana Hadzic Noémie Druelle Tiziana Napolitano Sergi Navarro-Sanz Serena Silvano Keith Al-Hasani Anja Pfeifer Sandra Lacas-Gervais Gunter Leuckx Laura Marroquí Julien Thévenet Ole Dragsbaek Madsen Patrick Collombat 《Cell》2017,168(1-2):73-85.e11
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Hao Jia Oleg M. Pustovyy Paul Waggoner Ronald J. Beyers John Schumacher Chester Wildey Jay Barrett Edward Morrison Nouha Salibi Thomas S. Denney Vitaly J. Vodyanoy Gopikrishna Deshpande 《PloS one》2014,9(1)
We depend upon the olfactory abilities of dogs for critical tasks such as detecting bombs, landmines, other hazardous chemicals and illicit substances. Hence, a mechanistic understanding of the olfactory system in dogs is of great scientific interest. Previous studies explored this aspect at the cellular and behavior levels; however, the cognitive-level neural substrates linking them have never been explored. This is critical given the fact that behavior is driven by filtered sensory representations in higher order cognitive areas rather than the raw odor maps of the olfactory bulb. Since sedated dogs cannot sniff, we investigated this using functional magnetic resonance imaging of conscious dogs. We addressed the technical challenges of head motion using a two pronged strategy of behavioral training to keep dogs'' head as still as possible and a single camera optical head motion tracking system to account for residual jerky movements. We built a custom computer-controlled odorant delivery system which was synchronized with image acquisition, allowing the investigation of brain regions activated by odors. The olfactory bulb and piriform lobes were commonly activated in both awake and anesthetized dogs, while the frontal cortex was activated mainly in conscious dogs. Comparison of responses to low and high odor intensity showed differences in either the strength or spatial extent of activation in the olfactory bulb, piriform lobes, cerebellum, and frontal cortex. Our results demonstrate the viability of the proposed method for functional imaging of the olfactory system in conscious dogs. This could potentially open up a new field of research in detector dog technology. 相似文献
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Friel Bouzid Imen Gtif Suad Alfadhli Salma Charfeddine Walid Ghorbel Rania Abdelhdi Riadh Benmarzoug Leila Abid Nouha Bouayed Abdelmoula Ins Elloumi Saber Masmoudi Ahmed Rebai Najla Kharrat 《Bioscience reports》2022,42(7)
The coronary artery disease (CAD) is a chronic inflammatory disease involving genetic as well as environmental factors. Recent evidence suggests that the oral microbiome has a significant role in triggering atherosclerosis. The present study assessed the oral microbiome composition variation between coronary patients and healthy subjects in order to identify a potential pathogenic signature associated with CAD. We performed metagenomic profiling of salivary microbiomes by 16S ribosomal RNA (rRNA) next-generation sequencing. Oral microbiota profiling was performed for 30 individuals including 20 patients with CAD and ten healthy individuals without carotid plaques or previous stroke or myocardial infarction.We found that oral microbial communities in patients and healthy controls are represented by similar global core oral microbiome. The predominant taxa belonged to Firmicutes (genus Streptococcus, Veillonella, Granulicatella, Selenomonas), Proteobacteria (genus Neisseria, Haemophilus), Actinobacteria (genus Rothia), Bacteroidetes (genus Prevotella, Porphyromonas), and Fusobacteria (genus Fusobacterium, Leptotrichia). More than 60% relative abundance of each sample for both CAD patients and controls is represented by three major genera including Streptococcus (24.97 and 26.33%), Veillonella (21.43 and 19.91%), and Neisseria (14.23 and 15.33%).Using penalized regression analysis, the bacterial genus Eikenella was involved as the major discriminant genus for both status and Syntax score of CAD. We also reported a significant negative correlation between Syntax score and Eikenella abundance in coronary patients’ group (Spearman rho = −0.68, P=0.00094).In conclusion, the abundance of Eikenella in oral coronary patient samples compared with controls could be a prominent pathological indicator for the development of CAD. 相似文献
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Besma Lakhal Sonia Ben-Hadj-Khalifa Nouha Bouali Pascal Philipert Françoise Audran Rim Braham Elghezal Hatem Charles Sultan Ali Saad 《Gene》2012
Background
WNT4 and SF1 genes play an important role in ovarian development. They constitute coherent candidate genes associated with premature ovarian failure (POF) pathogenesis.Methods
We sequenced the coding region of WNT4 and SF1 in 55 Tunisian women with POF and 100 healthy controls.Results
We identified a synonymous variation in WNT4 (c.99G>A, p.Ser33Ser) and a substitution (c.G437C) in SF1 gene inducing G146 to Ala (GGG–GCG) missense mutation. WNT4 (c.99G>A, p.Ser33Ser) was not associated with POF pathology. However, a positive association of SF1 Gly146Ala polymorphism was noted. Gly146Ala minor allele frequency was significantly higher (p = 0.029) in POF patients versus controls and Ala allele containing genotypes (p = 0.005) were positively associated with POF pathology. The carriage of 146Ala allele was also associated with a significant reduction in estradiol plasma levels.Conclusions
SF1 Gly146Ala polymorphism seems to be associated with POF pathology in the Tunisian population likely by reducing estradiol levels. 相似文献8.
Leila Ammar-Keskes Nozha Chakroun Afifa Sellami Ben Hamida Lobna Hadj-Kacem Nouha Bouayed-Abdelmoula Hammadi Ayadi Mohamed Nabil Mhiri Tarek Rebai Ali Bahloul 《Andrologie》2007,17(1):71-79
Objective
It is now very important to investigate azoospermia because the introduction of the intracytoplasmic sperm injection technique during the last decade has allowed many infertile men to achieve their dreams of fatherhood. The purpose of this study was to define the characteristics of infertile men with azoospermia, and to analyse the clinical and laboratory features and the causes of infertility in Tunisia. The authors also discuss various aspects that they consider to be very important in the diagnosis of male fertility.Material and Methods
This retrospective study analysed the parameters of physical examination, laboratory tests, semen analysis, radiographic examinations, testicular biopsy, karyotype and AZF microdeletions.Results
Based on the results of endocrinological and cytogenetic examinations, the aetiology of azoospermia was considered to be secretory in 43 cases of azoospermia. Physical examination revealed a high percentage of hypotrophic/atrophic testes (43.9%). Serum follicle stimulating hormone levels were high in 58.5% of cases. The overall incidence of chromosomal abnormalities was 31.4%. The most frequent anomaly was Klinefelter syndrome (9 cases). Seven out of 28 patients (25%) with nonobstructive azoospermia had AZF deletions. None of the patients with excretory azoospermia and severe oligospermia had an abnormal karyotype or AZF microdeletions. 48.8% of patients presented a varicocele, 13.9% had cryptorchidism and 13.0% had a history of genital tract infection.Conclusion
In line with the literature, genetic abmormalities are the main causes of severe forms of impaired spermatogenesis in the Tunisian population. 相似文献9.
Cytogenetics and fluorescence in situ hybridization assessment of sex-chromosome mosaicism in Klinefelter's syndrome 总被引:2,自引:0,他引:2
Abdelmoula NB Amouri A Portnoi MF Saad A Boudawara T Mhiri MN Bahloul A Rebai T 《Annales de génétique》2004,47(2):163-175
A retrospective study was carried out in 152 infertile men to determine the prevalence of sex chromosome abnormalities among non-obstructive azoospermic and severe oligospermic men (n = 51) and to evaluate the feasibility of fluorescence in situ hybridization (FISH) techniques to assess mosaicism in Klinefelter's patients in comparison with conventional cytogenetics. Cytogenetic analysis were performed for 51 infertile men and among 14 chromosomal abnormalities found, nine were compatible with Klinefelter's syndrome. FISH staining with a CEP X/CEP Y probes were performed for Klinefelter's patients and for five of them; testes were biopsied for histopathologic examination. Six Klinefelter's patients showed a non-mosaic 47,XXY and three showed a 47,XXY/46,XY mosaic by G or R banding analysis of 20 cells with a ratio of 17%, 20% and 33%, respectively. FISH analysis confirmed mosaicism in only one patient (the first) in whom a third cells population was found. There was no relationship between the ratios of mosaicism by banding and FISH analysis. Conventional histopathologic findings in five non-mosaic Klinefelter's patients confirm the diagnosis of Sertoli Only Cells syndrome. FISH is recommended in Klinefelter's syndrome to define exactly the cytogenetic statute as mosaic or non-mosaic and then discussing prognosis and decision regarding fertility counseling. 相似文献
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Bouayed Abdelmoula N Portnoi MF Keskes L Recan D Bahloul A Boudawara T Saad A Rebai T 《Annales de génétique》2003,46(1):11-18
XX maleness is the most common condition in which testes develop in the absence of a cytogenetically detectable Y chromosome. Using fluorescence in situ hybridization (FISH) or PCR, it was possible to detect the transfer of Yp fragments including SRY gene to the terminal part of X chromosome in the majority of XX males. We report a 32-year-old-male in whom a seminal analysis showed azoospermia, an X chromatin analysis showed 44% of Barr body positive nuclei and a chromosomal analysis revealed a 46,XX karyotype. Physical examination showed a normal sexual development and bilateral small testes. Hormonal studies revealed hypergonadotropic hypogonadism. Testis histological examination showed a profile of Sertoli Only Cell Syndrome. FISH study ruled out the presence of a Y-bearing cell line, and confirmed translocation of SRY to Xp terminal part. In order to confirm that the complete masculinized phenotype was related to a preferential inactivation of the no rearranged X chromosome, X-chromosome inactivation patterns (XCIP) were studied by analysis of methylation status of the androgen receptor gene. Highly skewed XCIP was observed by greater than 90% preferential inactivation involving one of the two X chromosomes, suggesting that the SRY-bearing X chromosome was the preferentially active X allowing for sufficient SRY expression for complete masculinization. 相似文献