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91.
Schmitt KC Zhen J Kharkar P Mishra M Chen N Dutta AK Reith ME 《Journal of neurochemistry》2008,107(4):928-940
The widely abused psychostimulant cocaine is thought to elicit its reinforcing effects primarily via inhibition of the neuronal dopamine transporter (DAT). However, not all DAT inhibitors share cocaine's behavioral profile, despite similar or greater affinity for the DAT. This may be due to differential molecular interactions with the DAT. Our previous work using transporter mutants with altered conformational equilibrium (W84L and D313N) indicated that benztropine and GBR12909 interact with the DAT in a different manner than cocaine. Here, we expand upon these previous findings, studying a number of structurally different DAT inhibitors for their ability to inhibit [(3)H]CFT binding to wild-type, W84L and D313N transporters. We systematically tested structural intermediates between cocaine and benztropine, structural hybrids of benztropine and GBR12909 and a number of other structurally heterologous inhibitors. Derivatives of the stimulant desoxypipradrol (2-benzhydrylpiperidine) exhibited a cocaine-like binding profile with respect to mutation, whereas compounds possessing the diphenylmethoxy moiety of benztropine and GBR12909 were dissimilar to cocaine-like compounds. In tests with specific isomers of cocaine and tropane analogues, compounds with 3alpha stereochemistry tended to exhibit benztropine-like binding, whereas those with 3beta stereochemistry were more cocaine-like. Our results point to the importance of specific molecular features--most notably the presence of a diphenylmethoxy moiety--in determining a compound's binding profile. This study furthers the concept of using DAT mutants to differentiate cocaine-like inhibitors from atypical inhibitors in vitro. Further studies of the molecular features that define inhibitor-transporter interaction could lead to the development of DAT inhibitors with differential clinical utility. 相似文献
92.
Seung Hyung Lee Prashant Shinde Jaeyong Choi Munsu Park Seho Ohh Ill Kyong Kwon Son Il Pak Byung Jo Chae 《Biological trace element research》2008,126(1):57-68
An experiment was conducted in weanling pigs (Landrace × Yorkshire × Duroc) to evaluate the effects of dietary iron levels on growth performance, hematological status, liver mineral concentration, fecal microflora, and diarrhea incidence. One hundred and forty-four piglets (initial BW 5.96 ± 0.93kg) were randomly allotted to one of the four dietary treatments on the basis of their body weights. The basal diets for each phase (phase 1: days0 to 14; phase 2: days15 to 28) were formulated to contain minimal Fe and then supplemented with gradient levels of Fe (0, 50, 100, and 250mg/kg) from ferrous sulfate. Feces were collected on days14 and 28 and used for the analysis of microbial count and trace minerals. Eight piglets from each treatment (two piglets per pen) were bled at 0, 7, 14, 21, and 28days to determine their hematological and plasma Fe status. In addition, two piglets from each pen (eight piglets per treatment) were killed at days14 and 28 to determine liver mineral concentrations. Pigs fed supplemental 250ppm Fe showed lowest overall average daily gain (linear, p = 0.036). Diarrhea incidence was linearly increased (p < 0.001) with supplemental Fe level. On days14, coliform population in normal feces was increased (p = 0.036) linearly with supplemental Fe level, and there were higher (p = 0.043) coliform population and lower (p < 0.001) Bifidobacterium spp. in the diarrhea feces. Supplemental Fe linearly (p < 0.05) improved the total red blood cells, hemoglobin, plasma, and liver (p = 0.109) Fe status of pigs and also increased (linear and quadratic, p < 0.001) the fecal excretion of Fe on days14 and 28. It is concluded that increasing the dietary iron levels in piglets improved their hematological status and liver Fe content; however, higher dietary Fe levels might also be associated with the increased diarrhea incidence. 相似文献
93.
Prashant K. DEEPAK Uttam K. SARKAR Raje S. NEGI Samir K PAUL 《动物学报》2008,54(1):136-143
为了获得印度北部赣达(Ganga)盆地河流中野生卡特拉鲃种群的年龄结构和重要生长参数,对该鱼的年龄和生长进行了研究。鳞片取自商业捕捞和实验室饲养的样品。根据研究分析,该鱼最大年龄可达8龄;巴吉拉蒂河(Bhagirathi R.)的种群平均体长为521.51 mm,退算体长为288.9 -1132.3 mm;旁遮普邦(Punjab)Satluj河种群平均体长为641.6 mm,退算体长为335.4 -1096.08 mm。2龄时,种群线性生长率(Cl)和体重增加率(Cw)表现出迅速下降的趋势。其它生长参数值(Clt)也呈现快速下降。退算体长差异(ANOVA)分析显示,生活在赣达盆地不同流域中的种群, 1^+-4^+龄组的长度差异较明显(P〈0.05) ,高龄组(5^+-8^+)差异不显著。根据本项研究结果,提出了对印度北部赣达盆地相关河流中生活的野生卡特拉鲃种群资源持续利用的对策。 相似文献
94.
Mutations in C2orf37, Encoding a Nucleolar Protein, Cause Hypogonadism, Alopecia, Diabetes Mellitus, Mental Retardation, and Extrapyramidal Syndrome
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Anas M. Alazami Amr Al-Saif Abdulaziz Al-Semari Saeed Bohlega Soumaya Zlitni Fatema Alzahrani Prashant Bavi Namik Kaya Dilek Colak Hanif Khalak Andy Baltus Borut Peterlin Sumita Danda Kailash P. Bhatia Susanne A. Schneider Nadia Sakati Christopher A. Walsh Futwan Al-Mohanna Brian Meyer Fowzan S. Alkuraya 《American journal of human genetics》2008,83(6):684-691
Hypogonadism, alopecia, diabetes mellitus, mental retardation, and extrapyramidal syndrome (also referenced as Woodhouse-Sakati syndrome) is a rare autosomal recessive multisystemic disorder. We have identified a founder mutation consisting of a single base-pair deletion in C2orf37 in eight families of Saudi origin. Three other loss-of-function mutations were subsequently discovered in patients of different ethnicities. The gene encodes a nucleolar protein of unknown function, and the cellular phenotype observed in patient lymphoblasts implicates a role for the nucleolus in the pathogenesis of this disease. Our findings expand the list of human disorders linked to the nucleolus and further highlight the developmental and/or maintenance functions of this organelle. 相似文献
95.
96.
Robert L. Seymour Prashant V. Mishra M. Akbar Khan & Michael P. Spector 《Molecular microbiology》1996,20(3):497-505
The starvation-stress response (SSR) of Salmonella typhimurium encompasses the physiological changes that occur upon starvation for an essential nutrient, e.g. C-source. A subset of SSR genes, known as core SSR genes, are required for the long-term starvation survival of the bacteria. Four core SSR loci have been identified in S. typhimuriumrpoSstiAstiB, and stiC. Here we report that in S. typhimurium C-starvation induced a greater and more sustainable cross-resistance to oxidative challenge (15 mM hydrogen peroxide (H2O2) for 40 min) than either N- or P-starvation. Of the four core SSR loci, only rpoS and stiC mutants exhibited a defective C-starvation-inducible cross-resistance to H2O2 challenge. Interestingly, (unadapted) log-phase S. typhimurium rpoS and stiA mutants were very sensitive to oxidative challenge. Based on this, we determined if these core SSR loci were important for H2O2 resistance developed during a 60 min adaptive exposure to 60 μM H2O2 (adapted cells). Both unadapted and adapted rpoS and stiA mutants were hypersensitive to a H2O2 challenge. In addition, a stiB mutant exhibited normal adaptive resistance for the first 20 mins of H2O2 challenge but then rapidly lost viability, declining to a level of about 1.5% of the wild-type strain. The results of these experiments indicate that: (i) the rpoS and stiC loci are essential for the development of C-starvation-inducible cross-resistance to oxidative challenge, and (ii) the rpoSstiA, and, in a delayed effect, stiB loci are needed for H2O2-inducible adaptive resistance to oxidative challenge. Moreover, we found that both stiA and stiB are induced by a 60 μM H2O2 exposure, but only stiA was regulated (repressed) by (reduced form) OxyR. 相似文献
97.
Currently, hyperhomocysteinemia is a well-known risk factor for variety of vascular diseases. Prevalence of
hyperhomocysteinemia increases with age. Hence, the present study was aimed to investigate the prevalence of
hyperhomocysteinemia in healthy upper socio-economic class population in India. Total homocysteine (tHcy) concentration was
determined in 1243 (906 men & 337 women) healthy Indian doctors with different age group. Using Third National Health and
Nutrition Examination Survey (NHANES III) study criteria, the prevalence of hyperhomocysteinemia was 92.85% among men
(>11.4 µmol/L) and 81.60% among women (>10.4 µmol/L). The prevalence of hyperhomocysteinemia was higher among men with
mean tHcy concentration (21.96 ± 0.38 µmol/L) significantly higher (P<0.0001) than women (15.90 ± 0.39 µmol/L) (95% CI, 4.733-
7.376). Our study showed very high prevalence of hyperhomocysteinemia which may point to the future risk for various
pathologies in the present subset of population. Further studies to look at the plasma levels of homocysteine lowering vitamins are
warranted to prevent the future risk of vascular diseases. 相似文献
98.
99.
Arenahalli Ningegowda Madhu Prashant Giribhattanavar Mandayam Singara Narayan Siddalingaiya Gurudutt Prapulla 《Biotechnology letters》2010,32(4):503-506
Vitamin B12 was produced by probiotic Lactobacillus plantarum in submerged fermentation (96 h) with successive anaerobic and aerobic phases of 48 h each to give 13 ng vitamin B12/g dry biomass. Sodium cyanide-mediated cell lysis, followed by benzyl alcohol/chloroform/water extraction, improved the release
of intracellular vitamin B12 for analysis. The presence of the K+ adduct of cyanocobalamin (m/z of 1394) was established using electron spray ionization–mass spectra; growth of a mutant of Escherichia coli in the presence of cyanocobalamin ascertained its bioavailability. 相似文献
100.
Pradhi Rajeev Prashant Rajput Dharmendra Kumar Singh Amit Kumar Singh 《人类与生态风险评估》2018,24(6):1453-1463
This study reports health risk assessment of PM1-bound carcinogenic hexavalent chromium [Cr(VI)] from central part of Indo-Gangetic plain (IGP) (PM1: particulate matter with aerodynamic diameter ≤1µm). Cr(VI) concentration has been estimated utilizing spectrophotometer with a modified novel method. Average ratio of Cr(VI)/CrT was 0.39 ± 0.07 (CrT: Total chromium) in the central IGP (Kanpur). Our study reports that mass fraction of Cr(VI) averaging at 0.39 is ~3 times higher than that assumed conventionally [Cr(VI)/CrT: 1/7]. Cancer risk assessment has been performed by assessing excess cancer risk (ECR) for the Cr(VI). ECR determined due to Cr(VI) was 57 and 14.3 (in one million) for adults and children, respectively. Our study suggests that risk due to Cr(VI) reported in previous studies were being underestimated by a factor of three. The Cr(VI)/CrT average ratio of 0.39 determined in this study was utilized to calculate risk assessment due to Cr(VI) from other locations in the IGP. Owing to large population of India (~125 million), the cancer risk due to Cr(VI) inhalation itself would become very significant. Thus, future research should focus on metal speciation of PM-bound samples from different locations to better constraint the toxicological risk assessment on a regional-to-global scale. 相似文献