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Complex Interplay between Sphingolipid and Sterol Metabolism Revealed by Perturbations to the Leishmania Metabolome Caused by Miltefosine
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With the World Health Organization reporting over 30,000 deaths and 200,000 to 400,000 new cases annually, visceral leishmaniasis is a serious disease affecting some of the world's poorest people. As drug resistance continues to rise, there is a huge unmet need to improve treatment. Miltefosine remains one of the main treatments for leishmaniasis, yet its mode of action (MoA) is still unknown. Understanding the MoA of this drug and parasite response to treatment could help pave the way for new and more successful treatments for leishmaniasis. A novel method has been devised to study the metabolome and lipidome ofLeishmania donovaniaxenic amastigotes treated with miltefosine. Miltefosine caused a dramatic decrease in many membrane phospholipids (PLs), in addition to amino acid pools, while sphingolipids (SLs) and sterols increased.Leishmania majorpromastigotes devoid of SL biosynthesis through loss of the serine palmitoyl transferase gene (ΔLCB2) were 3-fold less sensitive to miltefosine than wild-type (WT) parasites. Changes in the metabolome and lipidome of miltefosine-treatedL. majormirrored those ofL. donovani. A lack of SLs in the ΔLCB2 mutant was matched by substantial alterations in sterol content. Together, these data indicate that SLs and ergosterol are important for miltefosine sensitivity and, perhaps, MoA.

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Publication Date
Sun Jul 01 2018
Journal Name
Journal Of Educational And Psychological Researches
The Use of Discourse Markers by Iraqi Secondary Schools Pupils
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This research aims at investigating pupils’ ability in using discourse markers which are identified in the English textbooks of secondary schools. Four texts are chosen from third intermediate class. The four texts are short stories of different topics.                                                  

        This research hypothesizes that there are no statistical significant differences among Iraqi intermediate pupils’ ability in using textual

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Publication Date
Sun Dec 01 2024
Journal Name
Anbar Journal Of Agricultural Sciences
IMPROVING THE QUALITY OF POTATO MINI TUBERS BY SUSTAINABLE CULTIVATION
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Publication Date
Thu Mar 01 2007
Journal Name
Al-khwarizmi Engineering Journal
The Inverse Solution Of Dexterous Robot By Using Neural Networks
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The inverse kinematics of redundant manipulators has infinite solutions by using conventional methods, so that, this work presents applicability of intelligent tool (artificial neural network ANN) for finding one desired solution from these solutions. The inverse analysis and trajectory planning of a three link redundant planar robot have been studied in this work using a proposed dual neural networks model (DNNM), which shows a predictable time decreasing in the training session. The effect of the number of the training sets on the DNNM output and the number of NN layers have been studied. Several trajectories have been implemented using point to point trajectory planning algorithm with DNNM and the result shows good accuracy of the end

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Publication Date
Wed Jul 24 2024
Journal Name
Annals Of Parasitology
In vitro efficacy of different concentrations of lupeol on old world Leishmania donovani
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Leishmaniosis is a tropical neglected parasitic disease that is endemic in many countries, including Middle East, with no existing effective vaccines. The bite of female sand-fly transmits the causative agent, Leishmania spp., to humans. High toxicity, resistance and treatment failure of the available chemotherapy against visceral leishmaniosis demands the investigation of new anti-leishmanial compounds. Lupeol is a form of triterpene isolated from several medicinal plants and possesses an antimicrobial property. In this study, cytotoxic effect of lupeol was screened against the mammalian amastigotes form and insect promastigote form of Leishmania donovani, following three cycles of incubation at different concentrations by MTT assay. Resul

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Publication Date
Fri Oct 02 2026
Journal Name
Research Journal Of Pharmacy And Technology
Ex vivo study of anti-leishmanial activity of artemisinin against Leishmania tropica amastigote
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Leishmania parasites are the causative agent of leishmaniasis. Many studies are inspecting chemical drugs, including the use of miltefosine and amphotericin B, but curative values may be limited for these drugs with side effects due to the chemical origin, therefore, investigating less toxic therapies is essential. The aim of this study was to investigate the effectiveness of artemisinin on Iraqi strain of Leishmania tropica, by experimental macrophage ex vivo infection of amastigotes into mouse macrophage cell-line RAW264.7. Different concentrations (100, 200, 300, 400, 500)μM of artemisinin (ART) were screened to examine the susceptibility of L. tropica amastigotes to invade macrophage cell line along three times of follow up (24, 48 and

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Publication Date
Sun Jun 01 2014
Journal Name
International Journal Of Biological & Pharmaceutical Research
PROMASTIGOTES VIABILITY OF LEISHMANIA MAJOR W.T. ANDL. MAJOR KNOCKOUT LMLCB2 AFTER MYRIOCIN TREATMENT
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Sphingolipids (SLs) are major structural constituents of eukaryotes, including the kinetoplastid parasite Leishmania. SLs are important for cellular trafficking and signaling and participate in different cell functions, such as, differentiation and cell death (apoptosis). In this study we have investigated the viability of Leishmania major wild type (W.T) and L. major knockout LmLCB2, one of two subunits of serine palmitoyl transferase (SPT) after treatment with myriocin (potent inhibitor of SPT) in order to detect the survival and proliferation of the parasites in vitro. This is to focus on the de novo sphingolipids biosynthesis pathway in both Leishmania wild type which can synthesize SPT and knockout Leishmania which genetically ablated

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Publication Date
Wed Sep 16 2020
Journal Name
Research Journal Of Pharmacy And Technology
Ex vivo study of anti-leishmanial activity of artemisinin against Leishmania tropica amastigote
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Leishmania parasites are the causative agent of leishmaniasis. Many studies are inspecting chemical drugs, including the use of miltefosine and amphotericin B, but curative values may be limited for these drugs with side effects due to the chemical origin, therefore, investigating less toxic therapies is essential. The aim of this study was to investigate the effectiveness of artemisinin on Iraqi strain of Leishmania tropica, by experimental macrophage ex vivo infection of amastigotes into mouse macrophage cell-line RAW264.7. Different concentrations (100, 200, 300, 400, 500)μM of artemisinin (ART) were screened to examine the susceptibility of L. tropica amastigotes to invade macrophage cell line along three times of follow up (24, 48 and

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Publication Date
Mon Oct 01 2018
Journal Name
Journal Of Economics And Administrative Sciences
Alternative security solutions offered by virtual private network vpn model proposal to use alternatives to Cisco and Microsoft security in al-rasheed bank-delegate general office- northern region
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The study aims to provide a Suggested model for the application of Virtual Private Network is a tool that used to protect the transmitted data through the Web-based information system, and the research included using case study methodology in order to collect the data about the research area ( Al-Rasheed Bank) by using Visio to design and draw the diagrams of the suggested models and adopting the data that have been collected by the interviews with the bank's employees, and the research used the modulation of data in order to find solutions for the research's problem.

The importance of the study Lies in dealing with one of the vital topics at the moment, namely, how to make the information transmitted via

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Publication Date
Sun Mar 06 2016
Journal Name
Baghdad Science Journal
Investigation of the dielectric Properties of (PPAB) terminated by phenylenediamine doped by Na2[Fe(CN)5.NO].2H2O using Lumped equivalent circuit
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The aim of this paper is to demonstrate the effect of Na2[Fe(CN)5.NO].2H2O impurity (0.1 M) concentration on the dielectrical properties of poly (P-Aminobenzaldehyde) terminated by pheneylenediamine in the frequency and temperature ranges (1-100)KHz and (283-348) K respectively.These properties include dissipation factor, series and parallel resistance, series and parallel capacitance, real and imaginary part of the dielectric constant, a.c conductivity and impedance (real and imaginary) part, that have been deduced from equivalent circuit. The investigation shows that adding Na2[Fe(CN)5.NO].2H2O as additive to the polymer lead to increase of the dielectric constant with increasing temperature and it is decreasing with increasing the freq

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Publication Date
Sun Oct 01 2023
Journal Name
Minerva Dental And Oral Science
Salivary interleukin-1β as a biomarker to differentiate between periodontal health, gingivitis, and periodontitis
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