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101.
Imen Chamkha Emna Mkaouar-Rebai Hajer Aloulou Imen Chabchoub Chamseddine Kifagi Nourhene Fendri-Kriaa Thouraya Kammoun Mongia Hachicha Faiza Fakhfakh 《Biochemical and biophysical research communications》2011,(1):504
Mitochondria are essential for early cardiac development and impaired regulation of mitochondrial function was implicated in congenital heart diseases. We described a newborn girl with hypertrophic cardiomyopathy and profound hearing loss. The mtDNA mutational analysis revealed the presence of known polymorphisms associated to cardiomyopathy and/or hearing loss, and 2 novel heteroplasmic mutations: m.3395A > G (Y30C) occurring in a highly conserved aminoacid of the ND1 gene and the m.4316A > G located in the residue A54 of the tRNAIle gene. These 2 novel variations were absent in 150 controls. All these variants may act synergistically and exert a cumulative negative effect on heart function to generate the cardiomyopathy. 相似文献
102.
Chamkha I Mkaouar-Rebai E Aloulou H Chabchoub I Kifagi C Fendri-Kriaa N Kammoun T Hachicha M Fakhfakh F 《Biochemical and biophysical research communications》2011,404(1):504-510
Mitochondria are essential for early cardiac development and impaired regulation of mitochondrial function was implicated in congenital heart diseases. We described a newborn girl with hypertrophic cardiomyopathy and profound hearing loss. The mtDNA mutational analysis revealed the presence of known polymorphisms associated to cardiomyopathy and/or hearing loss, and 2 novel heteroplasmic mutations: m.3395A>G (Y30C) occurring in a highly conserved aminoacid of the ND1 gene and the m.4316A>G located in the residue A54 of the tRNA(Ile) gene. These 2 novel variations were absent in 150 controls. All these variants may act synergistically and exert a cumulative negative effect on heart function to generate the cardiomyopathy. 相似文献
103.
The protein kinase C (PKC) family of serine/threonine kinases is an attractive drug target because of its involvement in the regulation of various cellular functions, including cell growth, differentiation, metabolism, and apoptosis. The endogenous PKC activator diacylglycerol contains two long carbon chains, which are attached to the glycerol moiety via ester linkage. Natural product curcumin (1), the active constituent of Curcuma L., contains two carbonyl and two hydroxyl groups. It modulates PKC activity and binds to the activator binding site (Majhi et al., Bioorg. Med. Chem.2010, 18, 1591). To investigate the role of the carbonyl and hydroxyl groups of curcumin in PKC binding and to develop curcumin derivatives as effective PKC modulators, we synthesized several isoxazole and pyrazole derivatives of curcumin (2-6), characterized their absorption and fluorescence properties, and studied their interaction with the activator-binding second cysteine-rich C1B subdomain of PKCδ, PKCε and PKCθ. The EC(50)s of the curcumin derivatives for protein fluorescence quenching varied in the range of 3-25 μM. All the derivatives showed higher binding with the PKCθC1B compared with PKCδC1B and PKCεC1B. Fluorescence emission maxima of 2-5 were blue shifted in the presence of the C1B domains, confirming their binding to the protein. Molecular docking revealed that hydroxyl, carbonyl and pyrazole ring of curcumin (1), pyrazole (2), and isoxazole (4) derivatives form hydrogen bonds with the protein residues. The present result shows that isoxazole and pyrazole derivatives bind to the activator binding site of novel PKCs and both carbonyl and hydroxy groups of curcumin play roles in the binding process, depending on the nature of curcumin derivative and the PKC isotype used. 相似文献
104.
Maalej E Chabchoub F Samadi A de los Ríos C Perona A Morreale A Marco-Contelles J 《Bioorganic & medicinal chemistry letters》2011,21(8):2384-2388
The synthesis and pharmacological evaluation of racemic 14-aryl-10,11,12,14-tetrahydro-9H-benzo[5,6]chromeno[2,3-b]quinolin-13-amines (19-28), prepared by Friedländer reaction of 3-amino-1-aryl-1H-benzo[f]chromene-2-carbonitriles (10-18) with suitable cycloalkanones is described. These molecules are potent, in the nanomolar range [IC50 (EeAChE) = 7-101 nM], and selective inhibitors of acetylcholinesterase (AChE). The most potent inhibitor, 4-(13-amino-10,11,12,14-tetrahydro-9H-benzo[5,6]chromeno[2,3-b]quinolin-14-yl)phenol (20) [IC50 (EeAChE) = 7 ± 2 nM] is four-fold more active than tacrine. Kinetic studies on compound 20 showed that this is a mixed-type inhibitor of EeAChE with a Ki of 5.00 nM. However, racemic 20 was unable to displace propidium iodide, suggesting that the inhibitor does not strongly bind to the peripheral anionic site (PAS) of AChE. Docking, molecular dynamics stimulations, and MM-GBSA calculations agree well with this behavior. 相似文献
105.
Kaneez Fatima Shilu Mathew Mohd Suhail Ashraf Ali Ghazi Damanhouri Esam Azhar Ishtiaq Qadri 《PloS one》2014,9(9)
The nonstructural protein 3 (NS3) of hepatitis C virus (HCV) helicase is believed to be essential for viral replication and has become an attractive target for the development of antiviral drugs. The study of helicase is useful for elucidating its involvement in positive sense single-stranded RNA virus replication and to serve as templates for the design of novel antiviral drugs. In recent years, several models have been proposed on the conformational change leading to protein movement and RNA unwinding. Some compounds have been recently reported to inhibit the helicase and these include small molecules, RNA aptamers and antibodies. The current study is designed to help gain insights for the consideration of potential inhibitors for Pakistani HCV NS3 helicase protein. We have cloned, expressed and purified HCV NS3 helicase from Pakistani HCV serum samples and determined its 3D structure and employed it further in computational docking analysis to identify inhibitors against HCV genotype 3a (GT3a),including six antiviral key molecules such as quercetin, beta-carotene, resveratrol, catechins, lycopene and lutein. The conformation obtained after docking showed good hydrogen bond (HBond) interactions with best docking energy for quercetin and catechins followed by resveratrol and lutein. These anti-helicase key molecules will offer an alternative attraction to target the viral helicase, due to the current limitation with the interferon resistance treatment and presences of high rate of resistance in anti-protease inhibitor classes. 相似文献
106.
107.
Shalfawi SA Sabbah A Kailani G Tønnessen E Enoksen E 《Journal of strength and conditioning research / National Strength & Conditioning Association》2011,25(11):3088-3092
The purpose of this study was to examine the relationship between vertical jump measures and sprint speed over 10, 20, and 40 m in professional basketball players. Thirty-three professional basketball players aged (±SD) (27.4 ± 3.3 years), body mass (89.8 ± 11.1 kg), and stature (192 ± 8.2 cm) volunteered to participate in this study. All participants were tested on squat jump, countermovement jump, and 40-m running speed. The results show that all jump measures in absolute terms were correlated significantly to running performance over 10-, 20-, and 40-m sprint times. None of the jumping performance peak powers and reactive strength were found to have a correlation to running speed times in absolute term. Furthermore, all jump height measures relative to body mass except reactive strength had a marked and significant relationship with all sprint performance times. The results of this study indicate that while there is a strong and marked relationship between 10-, 20-, and 40-m sprint, there is also a considerable variation within the factors that contribute to performance over these distances. This may indicate that, separate training strategies could be implemented to improve running speed over these distances. 相似文献
108.
Amraoui F Krida G Bouattour A Rhim A Daaboub J Harrat Z Boubidi SC Tijane M Sarih M Failloux AB 《PloS one》2012,7(5):e36757
West Nile fever (WNF) and Rift Valley fever (RVF) are emerging diseases causing epidemics outside their natural range of distribution. West Nile virus (WNV) circulates widely and harmlessly in the old world among birds as amplifying hosts, and horses and humans as accidental dead-end hosts. Rift Valley fever virus (RVFV) re-emerges periodically in Africa causing massive outbreaks. In the Maghreb, eco-climatic and entomologic conditions are favourable for WNV and RVFV emergence. Both viruses are transmitted by mosquitoes belonging to the Culex pipiens complex. We evaluated the ability of different populations of Cx. pipiens from North Africa to transmit WNV and the avirulent RVFV Clone 13 strain. Mosquitoes collected in Algeria, Morocco, and Tunisia during the summer 2010 were experimentally infected with WNV and RVFV Clone 13 strain at titers of 10(7.8) and 10(8.5) plaque forming units/mL, respectively. Disseminated infection and transmission rates were estimated 14-21 days following the exposure to the infectious blood-meal. We show that 14 days after exposure to WNV, all mosquito st developed a high disseminated infection and were able to excrete infectious saliva. However, only 69.2% of mosquito strains developed a disseminated infection with RVFV Clone 13 strain, and among them, 77.8% were able to deliver virus through saliva. Thus, Cx. pipiens from the Maghreb are efficient experimental vectors to transmit WNV and to a lesser extent, RVFV Clone 13 strain. The epidemiologic importance of our findings should be considered in the light of other parameters related to mosquito ecology and biology. 相似文献
109.
Siala O Belguith N Kammoun H Kammoun B Hmida N Chabchoub I Hchicha M Fakhfakh F 《Gene》2012,507(1):68-73
Peters plus syndrome is an autosomal recessive rare disorder comprising ocular anterior segment dysgenesis, short stature, hand abnormalities, distinctive facial features, and often other major/minor additional defects. Peters plus syndrome is related to mutations in the B3GALTL gene with only seven recently reported mutations, leading to the inactivation of the B1, 3-glucosyltransferase. In this study, we screened the B3GALTL gene in two unrelated patients with typical Peters plus syndrome. A novel homozygous c.597-2A>G mutation was identified in both patients. Bioinformatic analyses showed that this mutation modulates the pre mRNA secondary structure of the gene, and decreases the score value related to the formation of splicing loops. Moreover, the c.597-2A>G mutation is located in a CpG Island of the B3GALTL gene, suggesting a potential epigenetic role of this position including gene's methylation and regulation. These data confirm an important role of the B3GALTL gene test that provides diagnosis confirmation and improves genetic counseling for the families. 相似文献
110.
M. A. Mseddi K. Chabchoub M. Bouasida N. Rebai M. Hadjslimen A. Bahloul M. N. Mhiri 《Andrologie》2012,22(1):42-45