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91.
Total synthesis,structural, and biological evaluation of stylissatin A and related analogs
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Farzana Shaheen Almas Jabeen Samreen Ashraf Muhammad Nadeem‐ul‐Haque Zafar Ali Shah Muhammad Asad Ziaee Nida Dastagir A. Ganesan 《Journal of peptide science》2016,22(9):607-617
The natural product cyclic peptide stylissatin A ( 1a ) was reported to inhibit nitric oxide production in LPS‐stimulated murine macrophage RAW 264.7 cells. In the current study, solid‐phase total synthesis of stylissatin A was performed by using a safety‐catch linker and yielded the peptide with a trans‐Phe7‐Pro6 linkage, whereas the natural product is the cis rotamer at this position as evidenced by a marked difference in NMR chemical shifts. In order to preclude the possibility of 1b being an epimer of the natural product, we repeated the synthesis using d ‐allo‐Ile in place of l ‐Ile and a different site for macrocyclization. The resulting product (d ‐allo‐Ile2)‐stylissatin A ( 1c ) was also found to have the trans‐Phe7‐Pro6 peptide conformations like rotamer 1b . Applying the second route to the synthesis of stylissatin A itself, we obtained stylissatin A natural rotamer 1a accompanied by rotamer 1b as the major product. Rotamers 1a , 1b , and the epimer 1c were separable by HPLC, and 1a was found to match the natural product in structure and biological activity. Six related analogs 2–7 of stylissatin A were synthesized on Wang resin and characterized by spectral analysis. The natural product ( 1a ), the rotamer ( 1b ), and (d ‐allo‐Ile2)‐stylissatin A ( 1c ) exhibited significant inhibition of NO.. Further investigations were focused on 1b , which also inhibited proliferation of T‐cells and inflammatory cytokine IL‐2 production. The analogs 2–7 weakly inhibited NO. production, but strongly inhibited IL‐2 cytokine production compared with synthetic peptide 1b . All analogs inhibited the proliferation of T‐cells, with analog 7 having the strongest effect. In the analogs, the Pro6 residue was replaced by Glu/Ala, and the SAR indicates that the nature of this residue plays a role in the biological function of these peptides. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
92.
Md Sainur Samad Lars R. Bakken Shahid Nadeem Timothy J. Clough Cecile A. M. de Klein Karl G. Richards Gary J. Lanigan Sergio E. Morales 《PloS one》2016,11(3)
Denitrification in pasture soils is mediated by microbial and physicochemical processes leading to nitrogen loss through the emission of N2O and N2. It is known that N2O reduction to N2 is impaired by low soil pH yet controversy remains as inconsistent use of soil pH measurement methods by researchers, and differences in analytical methods between studies, undermine direct comparison of results. In addition, the link between denitrification and N2O emissions in response to carbon (C) mineralization and pH in different pasture soils is still not well described. We hypothesized that potential denitrification rate and aerobic respiration rate would be positively associated with soils. This relationship was predicted to be more robust when a high resolution analysis is performed as opposed to a single time point comparison. We tested this by characterizing 13 different temperate pasture soils from northern and southern hemispheres sites (Ireland and New Zealand) using a fully automated-high-resolution GC detection system that allowed us to detect a wide range of gas emissions simultaneously. We also compared the impact of using different extractants for determining pH on our conclusions. In all pH measurements, soil pH was strongly and negatively associated with both N2O production index (IN2O) and N2O/(N2O+N2) product ratio. Furthermore, emission kinetics across all soils revealed that the denitrification rates under anoxic conditions (NO+N2O+N2 μmol N/h/vial) were significantly associated with C mineralization (CO2 μmol/h/vial) measured both under oxic (r2 = 0.62, p = 0.0015) and anoxic (r2 = 0.89, p<0.0001) conditions. 相似文献
93.
M N Younis H I Nadeem N el-MSalem A F Hamed A Ahmed G el-Masry A Hamza 《Journal of biosocial science》1987,19(3):305-311
This study was carried out in 4 adjacent villages in Lower Eghypt with a combined population of 24,000. A team of social workers and physicians worked together to introduce the injectable contraceptive depomedroxyprogesterone acetate as a post-partum long-acting contraceptive to the community leaders and the villagers at several meetings and individual home visits. Post-partum women who agreed to use the drug were defined as acceptors (591) and those who did not were defined as rejectors (715). The incidence of polygamy was higher among the rejectors, and rejectors' husbands had more children from their other wives. Acceptors had more previous pregnancies and children of both sexes than rejectors. The interval between the last 2 pregnancies was shorter among the rejectors. A greater % of acceptors had previously used another contraceptive. The commonest reasons for rejection were desire for further pregnancy (69%), health problems (11%), and desire for another method of contraception (8%). Religious factors figured in only 3% of cases. 相似文献
94.
Population viability analysis (PVA) entails calculation of extinction risk, as defined by various extinction metrics, for a study population. These calculations strongly depend on the form of the population growth model and inclusion of demographic and/or environmental stochasticity. Form of the model and its parameters are determined based on observed population time series data. A typical population time series, consisting of estimated population sizes, inevitably has some observation error and likely has missing observations. In this paper, we present a likelihood based PVA in the presence of observation error and missing data. We illustrate the importance of incorporation of observation error in PVA by reanalyzing the population time series of song sparrow Melospiza melodia on Mandarte Island, British Columbia, Canada from 1975–1998. Using Akaike information criterion we show that model with observation error fits the data better than the one without observation error. The extinction risks predicted by with and without observation error models are quite different. Further analysis of possible causes for observation error revealed that some component of the observation error might be due to unreported dispersal. A complete analysis of such data, thus, would require explicit spatial models and data on dispersal along with observation error. Our conclusions are, therefore, two‐fold: 1) observation errors in PVA matter and 2) integrating these errors in PVA is not always enough and can still lead to important biases in parameter estimates if other processes such as dispersal are ignored. 相似文献
95.
Fatemeh Rahimi Gharemirshamlu Maliha Afsar Taseem A. Mokhdomi Asif Amin Shoiab Bukhari Anbarasu Krishnan Chundi Vinay Kumar Kourosh Bamdad Trupti N. Patel Raies A. Qadri Naveed Anjum Chikan Nadeem Shabir 《Journal of cellular biochemistry》2019,120(5):7701-7710
Follicle-stimulating hormone-follicle-stimulating hormone receptor (FSH-FSHR) interaction is one of the most thoroughly studied signaling pathways primarily because of being implicated in sexual reproduction in mammals by way of maintaining gonadal function and sexual fertility. Despite material advances in understanding the role of point mutations, their mechanistic basis in FSH-FSHR signaling is still confined to mystically altered behavior of sTYS335 (sulfated tyrosine) yet lacking a substantial theory. To understand the structural basis of receptor modulation, we choose two behaviorally contradicting mutations, namely S128Y (activating) and D224Y (inactivating), found in FSH receptor responsible for ovarian hyperstimulation syndrome and ovarian dysgenesis, respectively. Using short-term molecular dynamics simulations, the atomic scale investigations reveal that the binding pattern of sTYS with FSH and movement of the thumb region of FSHR show distinct contrasting patterns in the two mutants, which supposedly could be a critical factor for differential FSHR behavior in activating and inactivating mutations. 相似文献
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99.
Nadeem N Woodside JV Kelly S Allister R Young IS McEneny J 《The Journal of nutritional biochemistry》2012,23(7):845-851
BackgroundVitamin E and its derivatives, namely, the tocopherols, are known antioxidants, and numerous clinical trials have investigated their role in preventing cardiovascular disease; however, evidence to date remains inconclusive. Much of the in vitro research has focused on tocopherol's effects during low-density lipoprotein (LDL) oxidation, with little attention being paid to very LDL (VLDL) and high-density lipoprotein (HDL). Also, it is now becoming apparent that γ-tocopherol may potentially be more beneficial in relation to cardiovascular health.ObjectivesDo α- and γ-tocopherols become incorporated into VLDL, LDL and HDL and influence their oxidation potential in an in vitro and ex vivo situation?DesignFollowing (i) an in vitro investigation, where plasma was preincubated with increasing concentrations of either α- or γ-tocopherol and (ii) an in vivo 4-week placebo-controlled intervention with α- or γ-tocopherol. Tocopherol incorporation into VLDL, LDL and HDL was measured via high-pressure liquid chromatography, followed by an assessment of their oxidation potential by monitoring conjugated diene formation.ResultsIn vitro: Both tocopherols became incorporated into VLDL, LDL and HDL, which protected VLDL and LDL against oxidation. However and surprisingly, the incorporation into HDL demonstrated pro-oxidant properties. Ex vivo: Both tocopherols were incorporated into all three lipoproteins, protecting VLDL and LDL against oxidation; however, they enhanced the oxidation of HDL.ConclusionsThese results suggest that α- and γ-tocopherols display conflicting oxidant activities dependent on the lipoprotein being oxidized. Their pro-oxidant activity toward HDL may go some way to explain why supplementation studies with vitamin E have not been able to display cardioprotective effects. 相似文献
100.
Saqib H. Ansari Tahir S. Shamsi Mushtaq Ashraf Tasneem Farzana Muneera Bohray Kousar Perveen Sajida Erum Iqra Ansari Muhammad Nadeem Ahmed Masood Ahmed Faizan Raza 《Indian journal of human genetics》2012,18(2):193-197