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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
Sat Jan 31 2026
Journal Name
Journal Of Physical Education
The impact of a training field in Lake Al-Razzaza to develop the strength of the legs and arms for young boxers
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Publication Date
Wed Jun 01 2022
Journal Name
Journal Of The College Of Languages (jcl)
Innovative approaches to the development of the lexical composition of the oil and gas industry : Инновационные подходы развития лексического состава нефтегазовой промышленности
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 The present study discusses one of the most relevant and required topics in the recent period during globalization, the modern Russian system of terms for the oil and gas industry as a whole acquired a complete form in the second half of the twentieth century. The period of the late XX - early XXI centuries. marked by cardinal transformations in all areas of the political, economic, social and cultural life of Russia. These changes could not but affect industrial production. Transition to a new vector of development of the Russian economy based on the development of commercial trade, on the change and improvement of the development of industrial enterprises in the context of the implementation of national projects and the introduction

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Publication Date
Thu Mar 21 2024
Journal Name
Nauchi From
METAPHORICAL APPROACH TO DESCRIBING THE MAIN CHARACTER IN THE NOVEL OF THE RUSSIAN WRITER L. ULITSKAYA "SINCERELY YOUR SHURIK": MEANING AND INFLUENCE
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The article reflects the results of the analysis of the use of metaphors as one of the main means used by Lyudmila Ulitskaya when writing the novel “Sincerely Yours Shurik” to form the image of the main hero in the novel. The main purpose of the article is to consider metaphors, which helped the author to form the image of the main character Shurik in the text space through the stages of his life path, closely related to the people around him, who is always happy to be useful (hence the title "Sincerely Yours"), among which the female images of his relatives, girlfriends and others stand out as a special layer in the narrative. And in the course of the study, the following tasks were solved: the metaphors that make up the image of the

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Publication Date
Mon Sep 12 2022
Journal Name
Communications In Mathematical Biology And Neuroscience
The influence of fear on the dynamic of an eco-epidemiological system with predator subject to the weak Allee effect and harvesting
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In this paper, an eco-epidemiological prey-predator system when the predator is subjected to the weak Allee effect, and harvesting was proposed and studied. The set of ordinary differential equations that simulate the system’s dynamic is constructed. The impact of fear and Allee’s effect on the system's dynamic behavior is one of our main objectives. The properties of the solution of the system were studied. All possible equilibrium points were determined, and their local, as well as global stabilities, were investigated. The possibility of the occurrence of local bifurcation was studied. Numerical simulation was used to further evaluate the global dynamics and understood the effects of varying parameters on the asymptotic behavior of t

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Publication Date
Wed Nov 01 2017
Journal Name
Journal Of Economics And Administrative Sciences
The role of administrative supervision scope and the single window to increase the efficiency of investment (Case study: Sudanese Ministry of Investment)
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Investment drives the wheel of the development of different developed and developing countries. Sudan is a model for a developing country facing a lot of difficulties in the field of both local and foreign investment. The present study was focused on the problem of poor diversification and efficiency of both local and foreign investment in Sudan. Also, it clarified the important role of administrative supervision to strengthen the efficiency of investment, taking the experience of the Sudan as a model. The researchers used the well-known descriptive and analytical tools (questionnaire, interview, observation) to complete this study. A well designed questionnaire was used. It included all questions that could cover all aspects of

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Publication Date
Sun May 01 2022
Journal Name
International Journal Of Early Childhood Special Education (int-jecs)
Study of some visual functions and functional variables of the respiratory and nervous systems and their relationship to the level of achievement of air rifle shooting
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The purpose of this paper is to identifying the relationship between some visual functions and the level of achievement of air rifle shooting among young Iraqi female, and identifying the relationship between some functional variables of the respiratory and nervous systems at the level of achievement of air rifle shooting among young Iraqi female. The researchers used the descriptive approach in the correlative relationships style for its suitability and the research problem. The researchers determined the research community by the intentional method represented by (10) young female shooters who represent the national team with air rifle shooting effectiveness, and who represent (100%) of the research community. One of the most important re

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Publication Date
Sat Feb 02 2019
Journal Name
Journal Of The College Of Education For Women
Suspicion in the truth that the satisfaction of the student in the criticism of the speech of the poet and the writer to I bin Al-Atheer
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Suspicion in the truth that the satisfaction of the student in the criticism of the speech of the poet and the writer to I bin Al-Atheer

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Publication Date
Sun Oct 07 2012
Journal Name
Journal Of Educational And Psychological Researches
Bullying and its relation to parental treatment style
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The current research aims to know the relationship between bullying and parental treatment. (200) pupils were selected randomly from the fifth and sixth grades of primary schools.

Two instruments were used. The first was to measure bullying and it included 19 items. To measure parental treatment, the researchers adopted (Aletaby 2001) scale.

Statistical analysis showed that correlation between bullying , wiggle and Firm treatment style was positive Statistically significant .Bulling was correlated negatively with (neglect, careless, and Authoritarian treatment style.

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Publication Date
Wed Jan 01 2020
Journal Name
Modern Sport
Special exercises according to the Dynafoot data and its effect on the force index and the performance of the front straight air flip skill on the ground movements mat device
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Publication Date
Thu Dec 29 2022
Journal Name
Arterial Hypertension
Correlation between coronary artery calcium score and aorta diameter in population with long-standing hypertension using noncontrast CT scan
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