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Insecticide resistance and Bionomics in laboratory reared and field caught Anopheles funestus Giles (Diptera: Culicidae)Spillings, Belinda Lea 23 January 2013 (has links)
Malaria is transmitted by the mature, blood feeding portion of mosquito vector populations. Malaria vector control programs based on indoor residual spraying (IRS) of insecticides are designed to target resting adult Anopheles mosquitoes before or after they have blood fed.
When a female mosquito acquires a blood meal, she could also ingest harmful xenobiotics that are present in the blood. During the resting period after feeding, many processes are initiated in order to assist in the digestion and assimilation of the blood. Ultimately, this enables the mosquito to absorb those amino acids needed for the biosynthesis of yolk proteins, which are essential for subsequent egg maturation. Since the regulation of xenobiotic (including insecticides) detoxification enzyme systems is likely to be altered in response to the ingestion of blood, this study aimed to investigate the effect of a blood meal on insecticide tolerance in insecticide resistant and susceptible southern African strains of the major malaria vector Anopheles funestus.
Through the use of CDC bottle bioassays it was demonstrated that blood fed An. funestus carrying a pyrethroid resistant phenotype are even more tolerant of pyrethroid intoxication than their unfed counterparts. Using another major malaria vector, An. gambiae, microarray analysis revealed that a general increase in delta class glutathione-s-transferase (GST) expression occured in response to a blood meal. One gene, GSTD3, was over-expressed in both blood fed An. gambiae and An. funestus. Although this gene could not be validated with real time quantitative PCR, it serves as a viable target for future investigations.
Since the pyrethroid resistant phenotype of southern African An. funestus has been linked to the over-expression of the duplicate copy gene CYP6P9, the expression levels of both copies of this gene were investigated. CYP6P9 and its copy, CYP6P13, showed a small but significant increase in expression in response to a blood meal. The increased expression of these major effect genes in response to blood feeding may be responsible for the increase in insecticide tolerance seen in the bottle bioassays.
In an effort to repeat these experiments on wild caught An. funestus, field material was collected from Karonga in northern Malawi. Specimens were morphologically identified as members of the An. funestus group. However, attempts to molecularly identify them to species level failed. Through the use of ITS2 and D3 sequence analysis, cytogenetics and cross mating studies it was possible to conclude that these wild caught specimens were a new species. They have been provisionally named An. funestus-like.
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The effects of pyrethroid resistance on transcription of metabolic enzymes in a major African Malaria vector, Anopheles funestusChristian, Riann N 11 January 2012 (has links)
Anopheles funestus is a major vector of malaria in the southern African region.
Insecticide resistance to pyrethroid and carbamate insecticides has been recorded in
populations of this species in South Africa and Mozambique. This study aimed to
determine the relationship between pyrethroid resistance and gene expression of two
closely related genes, CYP6P9 and CYP6P13, by age and sex in a resistant strain An.
funestus from southern Africa, FUMOZ-R. The insecticide susceptibility assays
showed that percentage survival in both FUMOZ-R sexes significantly decreased as
age increased. The mRNA expressions of CYP6P9 and CYP6P13 were higher in
FUMOZ-R relative to the insecticide susceptible strain (FANG). The expression of
permethrin resistance varies with age in An. funestus FUMOZ-R. The results indicate
that other genes may also be involved in insecticide resistance. In addition to this, the
expression profile of other metabolic genes involved in insecticide resistance was also
investigated. A microarray based approach was used to identify genes differentially
expressed in FUMOZ-R and FANG. As the full set of detoxification genes in An.
funestus are unknown, this study investigated the utility of the An. gambiae detox chip
to screen for differentially expressed detoxification genes in An. funestus. After
optimization of the hybridisation conditions, over 90% of the probes showed a
positive signal. Only three genes were significantly (P<0.001) differentially expressed
in the females, CYP6P9, COI and CYP6M7. The same genes were also significantly
differentially expressed in the adult males, together with an additional 21 transcripts.
The third part of this study investigated the gene expression in the first instar, fourth
instar and 3-day old adults in FUMOZ-R using the An. gambiae detox chip. The
variation in metabolic enzyme gene transcription at the different developmental stages in An. funestus are not known. The identification of differentially transcribed genes at
the different life stages provides some insight into the role and function of these
genes. A large number of cytochrome P450s (monooxygenases), esterases,
glutathione S-transferases (GSTs) and other additional genes were differentially
expressed in all life stages. This study provided vital information regarding genes
potentially involved in pyrethroid resistant and is the first to provide metabolic or
detoxifying transcription gene information in An. funestus.
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Efficacy of artemisinin derivatives in treating severe malaria in children: A systematic review and meta-analysisPraygod, George 01 November 2006 (has links)
Student Number : 0416598H -
MSc research report -
School of Public Health -
Faculty of Health Sciences / Background
Evidence shows that the efficacy of intravenous quinine, which is the mainstay for treating severe malaria in children, is decreasing. Artemisinin derivatives are the potential replacement for quinine. Their efficacy compared to quinine in treating severe malaria in children is not well known.
Objective
To assess the efficacy of parenteral artemisinin derivatives versus parenteral quinine in treating severe malaria in children.
Search strategy
The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2005), MEDLINE (1966 to October 2005), EMBASE (1980 to October 2005), and LILACS (1982 to October 2005) were searched. Malaria researchers and a pharmaceutical company were contacted. In addition, conference proceedings were also searched.
Selection criteria
Randomised controlled studies comparing parenteral artemisinin derivatives with parenteral quinine in treating severe malaria in children. All trials had to report mortality as an outcome.
Data collection
After data were extracted, two individuals independently assessed the trial quality. In addition, information on adverse effects from the studies was also collected.
Main results
Eleven trials were selected (1455 subjects), nine of them from Africa and the rest from Asia. Allocation concealment was adequate in seven trials (1238 subjects). Overall there was no difference in mortality between artemisinin derivatives and quinine (Risk Ratio= 0.89, 95% confidence interval 0.71 to 1.1). There was no difference in mortality between adequately concealed and inadequately concealed /unconcealed trials (Risk Ratio = 0.93, 95% confidence interval 0.74 to 1.16 and Risk Ratio=0.66, 95% confidence interval 0.36 to 1.22). In Parasite Clearance Time (PCT), though there was no statistical difference between the two groups there was a tendency towards favouring the artemisinin derivatives (weighted mean difference among studies which reported PCT as mean was -4.76 with 95% confidence interval -9.68 to 0.17 and all three studies which reported PCT as median showed that artemisinin derivatives cleared parasites faster than quinine, each had p<0.001). However; when only trials with adequate concealment were considered this potential advantage disappeared. In exploring heterogeneity for PCT, it was shown that study settings (Asia versus Africa) might have been a cause for heterogeneity. The artemisinin derivatives resolved coma faster than quinine (weighted mean difference=-5.32, 95%CI: -8.06 to -2.59), but when only trials with adequate concealment were considered this difference disappeared. Other secondary outcomes i.e. Fever clearance time, Incidence of neurological sequelae, and 28th day cure rate showed no significant difference between artemisinin derivatives and quinine. There was no enough data to make meaningful comparison of adverse effects between the two groups.
Conclusions
The available evidence suggests that parenteral artemisinin derivatives are as efficacious as quinine in preventing mortality from severe malaria in children.
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Insecticide resistance and vector status of Anopheles funestus and An. gambiae populations at a sugar estate in MozambiqueKloke, Ronald Graham 12 April 2010 (has links)
MSc (Med), Faculty of Health Sciences, University of the Witwatersrand, 2009 / Malaria is on the increase in Mozambique since 2001 and impacts primarily on
children < 5 years of age. Insecticide resistance in the malaria vector mosquitoes is on
the increase in Mozambique and Africa and is cause for serious concern. Maragra
sugar estate is situated in close proximity to the nKomati river floodplain in a rural
area in Mozambique and requires intense irrigation for cane growing and as a result
provides extensive breeding sites for An. funestus and other mosquitoes. In the areas
surrounding the estate there are two important vectors of malaria, Anopheles funestus
group and An. gambiae complex. There is intense malaria transmission in the areas
surrounding the sugar estate and the last entomological study on the vectors in the
Manhica area was done in 1998. It was becoming increasingly urgent to identify to
species level the vectors in this area and to monitor the insecticide resistance status of
these vectors. Due to leakage (theft) of insecticides and a change by the National
Malaria Control Programme (NMCP) to an insecticide to which the predominant
vector is resistant, an entomological survey was carried out in this area from January
2009 to March 2009 to ascertain by Polymerase chain reaction (PCR) what species of
malaria vectors were present inside and outside of the Maragra vector control area,
their population levels and their vectorial status in these two areas. Insecticide
resistance studies by insecticide exposure and the synergist piperonyl butoxide (pbo)
were carried out using the World Health Organisation (WHO) bioassay method on
collected An. funestus mosquitoes. This was done to establish this species resistance
status to the four classes of insecticides recommended by the WHO for malaria vector
control. The collections of An. arabiensis and An. merus that were identified were too
few to carry out insecticide resistance tests on these two species. Enzyme linked
v
immuno-sorbent assay (ELISA) tests were undertaken to establish the vectorial
capacity of Anopheles funestus and An. gambiae complex in this area. The
predominant malaria vector species in this area is An. funestus s.s., with the secondary
vector being An. arabiensis. An. funestus has a high vectorial capacity in this area and
found to have a Plasmodium falciparum sporozoite rate of 6.02%. This is an increase
in the sporozoite rate of 1.2% from 1998 when the last survey in this regard was
carried out. Coupled with this increase is an increase in the An. funestus populations
in this area since this time. One An. gambiae complex sample was found to be
positive but the species is not known as this particular sample did not amplify on
PCR. Anopheles funestus is highly resistant to synthetic pyrethroids and exhibits a
lower level of resistance to bendiocarb, a carbamate insecticide in use at Maragra
sugar estate. The synergist pbo mediates the resistance mechanism in both these
insecticides indicating that the metabolic resistance mechanism present in this
mosquito is strongly mediated by monooxygenase detoxification. The role of the
medical entomologist is increasingly necessary and important in the monitoring of this
resistance phenomenon in malaria vector mosquitoes, as is the role of the vector
control programme manager in implementing and managing vector control
programmes. The implication of cane sugar farming and its impact on vector
production and malaria transmission is discussed. Insecticide resistance and the
change by the NMCP to a synthetic pyrethroid to which the predominant vector of
malaria is resistant is discussed.
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Design and development of multifunctional Raman active noble metals nanoprobes for the detection of malaria and tuberculosis biomarkersMlambo, Mbuso January 2016 (has links)
A thesis submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy. Johannesburg, 2015. / Surface enhanced Raman spectroscopy (SERS) has emerged as a surface sensitive
vibrational technique that leads to the enhancement of the Raman scattering molecules on
or close to the surface of a plasmonic nanostructure. The enhancement is found to be in
orders of 104 to 1015, which allows the technique to be sensitive enough to detect a single
molecule.
In this study, we report on the synthesis of different sizes of gold and silver nanoparticles
(AuNPs and AgNPs) and gold nanorods (AuNRs). These are functionalized or co-stabilized
with different stoichiometric ratios of HS-(CH2)11-PEG-COOH and alkanethiols (Raman
reporters), i.e.; HS-(CH2)11-NHCO-coumarin(C), HS-(CH2)11-triphenylimidazole (TPI), HS-
(CH2)11-indole (HSI), HS-(CH2)11-hydroquinone (HQ) to form mixed monolayer protected
clusters (MMPCs). The alkanethiols were chosen as Raman reporters to facilitate the selfassembled
formation of monolayers on the metal surface, thus resulting in stable MMPCs.
The optical properties and stability of MMPCs were obtained using ultraviolet-visible (UVvis)
spectrophometry and a zeta sizer. Size and shape of the as-synthesized nanoparticles
were obtained using transmission electron microscopy (TEM). The tendency of thiolcapped
nanoparticles to form self-assembled ordered superlattices was observed. Their
Raman activities were evaluated using Raman spectroscopy, with the enhancement factor
(EF) being calculated from the intensities of symmetric stretch vibrations of C-H observed
in the region of about 2900 to 3000 cm-1 in all SERS spectra. In all four different
alkanethiols (Raman reporters), smaller size metal nanoparticles (14 nm for AuNPs and 16
nm AgNPs) showed higher EF compared to 30 and 40 nm metal nanoparticles. The EF
was observed to increase proportionally with stoichiometric ratios of alkanethiols from 1%
iv | P a g e
to 50%. The prepared MMPCs with small sizes were used as a SERS probe for the
detection of malaria and tuberculosis biomarkers.
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The Economics of Life and Death: Rethinking Our Battle with Malaria in a New Era of Disease ControlMeme, Kevin January 2003 (has links)
Thesis advisor: Anderson James / Malaria kills over 3,000 people each day—mostly in sub-Saharan Africa—and remains the world's number one killer of children under five. While efforts to combat the disease were largely successful in past decades, eradication has since stalled as the parasite (and its mosquito vector) have retreated to the core tropics and become increasingly resistant to pesticides and anti-malarial drugs. This study seeks to determine what other factors are significant in producing high malaria rates, and, based on those results, to offer policy suggestions that may provide alternatives to the “traditional” methods of combating malaria. The project uses cross-country models and individual country models of malaria output to analyze country indicator data and household survey data from around the world. Empirical analysis reveals that foreign aid flows may be less significant in reducing malaria outputs than originally suspected. Furthermore, the data suggests that other factors such as political stability, access to goods and services, and the use of bednets perhaps demand greater attention than they currently receive. / Thesis (BS) — Boston College, 2003. / Submitted to: Boston College. College of Arts and Sciences. / Discipline: Economics. / Discipline: College Honors Program.
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Malária autóctone notificada no Estado de São Paulo: aspectos clínicos e epidemiológicos, de 1980 a 2007 / Reported autochthonous malaria in São Paulo: clinical and epidemiological description, from 1980 to 2007Couto, Renata D\'Avila 03 February 2009 (has links)
Introdução: A malária autóctone no Estado de São Paulo (ESP) caracteriza-se por surtos esporádicos na região oeste e transmissão persistente na região leste onde ocorrem casos oligossintomáticos com baixa parasitemia pelo Plasmodium vivax. Objetivos: Analisar a completitude das fichas de notificação de malária autóctone; estimar a tendência da incidência de casos autóctones no ESP de 1980 a 2007; analisar o comportamento clínico e epidemiológico dos casos em duas regiões de autoctonia neste período. Métodos: Foi realizado um estudo descritivo com 19 variáveis das fichas de notificação de malária do ESP, analisadas em duas regiões e em dois períodos (1980-1993 e 1994-2007). Fontes de dados: SUCEN/SES/SP, SINAN/CVE/SES/SP e DATASUS. Resultados: A completitude foi superior a 85% em 11 variáveis. A tendência da incidência de malária autóctone no ESP foi decrescente. Foram notificados 821 casos de autoctonia, 91,6% na região leste, predominando P. vivax. A infecção assintomática teve maior porcentagem no segundo período (p<0,001). Discussão: A completitude das informações foi satisfatória. As diferenças clínicas encontradas merecem atenção da vigilância epidemiológica que deve lidar com o desafio da infecção assintomática por Plasmodium. / Introduction: Autochthonous malaria in São Paulo State is characterized by sporadic outbreaks in the west region and by persistent transmission with oligoassymptomatic cases in the east region, with low parasitemia by Plasmodium vivax. Objectives: To assess the completeness of autochthonous malaria reporting forms; to estimate autochthonous malaria incidence trends in São Paulo State from 1980 to 2007; to analyze the clinical and epidemiological patterns in two distinct regions of autochthony in this period. Methods: This was a descriptive study that analysed 19 report form variables, comparing the east and the west in two periods (1980-1993 and 1994-2007). Sources of secondary data: SUCEN/SES/SP, SINAN/CVE/SES/SP e DATASUS. Results: The completeness was over 85% on 11 variables. The autochthonous malaria incidence trend was decreasing. There were 821 cases of autochthony, 91.6% occurred in the east, predominantly caused by P. vivax. The asymptomatic infection had higher percentage in the second period (p <0.001). Discussion: The completeness of the information was satisfactory. The clinical differences observed deserve attention from surveillance that must deal with the challenge of asymptomatic infection by Plasmodium.
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Therapie der unkomplizierten Malaria tropica mit Chloroquin und Sulfadoxin-Pyrimethamin bei Kindern in Tamale, GhanaKnobloch, Andreas 17 August 2005 (has links)
Malaria ist noch immer die häufigste parasitäre Erkrankung in den Tropen. Vor allem afrikanische Kinder < 5 Jahren sind betroffen. Die steigende Chloroquinresistenz ist für einen deutlichen Anstieg der Kindersterblichkeit verantwortlich. Mehrere Studien belegen, dass die Kombination von Chloroquin (CQ) mit Sulfadoxin-Pyrimethamin (SP) in Afrika bei niedriggradiger CQ-Resistenz die therapeutische Wirksamkeit erhöht und damit auch die Resistenzentwicklung gegenüber beiden Medikamenten verzögern kann. Bei 315 Kindern im Alter von 6-59 Monaten wurde von Nov. 2000 bis Nov. 2001 eine Studie zur Epidemiologie der Malaria und zum Therapieausgang von CQ und SP in Tamale/Nord-Ghana durchgeführt. Bei Vorliegen einer Malaria wurde mit CQ und SP behandelt und der Therapieausgang gemäß eines modifizierten WHO-Protokolls von 1996 ermittelt. Die Gesamtzahl der Malaria-Episoden im Zeitraum betrug 836. In der Regenzeit erkrankte mit 23,7% ein signifikant höherer Anteil der Kinder an Malaria als in der Trockenzeit mit 9,4%. Ein frühes Therapieversagen (ETF) wurde in 5% der Fälle beobachtet, ein spätes Therapieversagen (LTF) in 19,5% der Fälle. 211 Fälle (68,7%) hatten einen klinischen Therapieerfolg (ACR). Alter < 3 Jahren war ein unabhängiger Einflussfaktor für ETF und Gesamttherapieversagen. Eine hohe Parasitendichte war ein unabhängiger Einflussfaktor für LTF und Gesamttherapieversagen. Das Risiko, ein Gesamttherapieversagen (ETF + LTF) zu entwickeln, war in der Regenzeit um das 6-fache gegenüber der Trockenzeit erhöht. Bei allen erstmalig mit CQ und SP behandelten Fällen (n = 206) war der ACR (72,3%) statistisch grenzwertig höher als bei zweiter oder mehrfacher Behandlung (61,4%; n = 101). Bei den mehrfach therapierten Fällen bestand mit 27% gegenüber 16% bei den erstmalig therapierten Fällen ein signifikant höheres Risiko, ein LTF zu entwickeln. Die Erholung des Hb-Gehalts bei den erfolgreich therapierten Fällen betrug 0,6 g/dl und unterschied sich signifikant vom Hb-Anstieg (0,4 g/dl) bei Fällen mit LTF. Ein Vergleich des ACR der beschriebenen Studie mit einer zuvor durchgeführten CQ-Studie ergab keinen signifikanten Unterschied. Die Ergebnisse dieser Studie legen die Schlussfolgerung nahe, dass sich die Therapie aus CQ und SP wegen der hohen CQ-Resistenz und der sich rasch entwickelnden SP-Resistenz zumindest in Nordghana nicht eignet. / Malaria remains the most frequent parasite disease in the tropics. Especially African children under 5 years are at risk. The rising chloroquine resistance is the cause for a significant increase in childhood mortality. Several studies indicate that the combination of chloroquin (CQ) and sulfadoxine-pyrimethamine (SP) in Africa with low-grade CQ resistance increases the therapeutic efficacy and can thus slow down the development of resistance to both drugs. The epidemiology of malaria and the therapeutic outcome of CQ and SP was assessed in a cohort study of 315 children aged 6-59 months from November 2000-November 2001 in Tamale/Northern Ghana. In the case of malaria a combination therapy of CQ and SP was given and the therapeutic outcome was assessed in a modified WHO protocol. The total number of all malaria episodes in the observation period was 836. In the rainy season, the amount of the children with malaria was significantly higher than in the dry season (23,7% vs. 9,4%). Early treatment failure (ETF) was observed in 5% of the cases and late treatment failure (LTF) in 19,5%. 211 cases (68,7%) fulfilled the criteria for adequate clinical response (ACR). Age under 3 years was an independent predictor for ETF and overall therapeutic failure. High initial parasite density was an independent predictor for LTF and overall therapeutic failure. The risk of developing an overall therapeutic failure (ETF + LTF) was 6 times greater in the rainy season than in the dry sason. In all cases with the first treatment of CQ and SP (n = 206), the percentage of ACR (72,3%) was significantly greater than in cases treated twice or more (61,4%, n = 101). Cases with 2 or more treatments were at a significantly higher risk of developing a LTF than cases with one treatment (27% vs. 16%). The recovery of the hb levels in cases with successful treatment was 0,6 g/dl and was significantly different from the haemoglobin increase in cases with LTF. A comparison between the therapeutic success of CQ and SP with CQ alone did not show a significant difference. The results of this study indicate that the combination therapy of CQ and SP is no longer useful for treatment of uncomplicated malaria in Northern Ghana because of the high CQ resistance and the increasing resistance of SP.
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Inter-relação do ritmo e da ação de drogas antimaláricas na infecção da malária de roedores / Relotronship between rhythm and antimalarial action in malaria injection of rodentsBagnaresi, Piero 17 April 2009 (has links)
A malária é a doença parasitaria que mais mata no mundo. Metade da população mundial está sob risco de contrair a doença, que mata mais de 1 milhão de pessoas por ano, principalmente crianças com menos de 5 anos de idade. A periodicidade das febres é o sintoma característico da doença. A febre é resultado da lise dos eritrócitos mediada pela saída do parasita, para infectar novas células. Esse evento é sincronizado, com os parasitas rompendo as células ao mesmo tempo. Para que isso aconteça, os eventos celulares que são necessários para a maturação do parasita dentro do eritrócito tem que ser finamente regulada. O hormônio circadiano melatonina é o sinal que sincroniza o ciclo intraeritrocítico do Plasmodium. Neste trabalho, reportamos que a sincronia observada na maioria das espécies do parasita pode ser usada por ele como meio de evadir o sistema imune do hospedeiro e assegurar a continuidade da infecção. Quando dessincronizamos o desenvolvimento do parasita P. chabaudi utilizando luzindol, um antagonista da melatonina, foi observado que o uso de uma dose sub-otima do antimalárico cloroquina aumenta a sobrevida de camundongos infectados. Reportamos também que P. berghei, parasita de roedor que possui uma infecção não sincronizada, não percebe o hormônio. Diferentemente do que é observado com espécies que possuem sincronia, a melatonina falhou em induzir aumento de cálcio intracelular ou sincronizar o ciclo de vida do parasita in vitro. No trabalho também é relatado a construção de vetores para nocauteamento de genes em Plasmodium, afim de se conhecer a função das genes alvo por análise de fenótipo. / Malaria is the most killing parasitic disease in the world. Half of the world population is at risk of contracting the disease, which kills over 1 million people, being children under 5 the most affected. The fever periodicity is the characteristic symptom of the disease. The fever is a result of the burst of the erythrocyte when the parasite leaves the host cell to infect other ones. This event is highly synchronous, with the parasites going out of the cells at the same time. For this to happen, the cellular events that are necessary for parasite growth have to be very well regulated. The circadian hormone melatonin is the signal that synchronizes the intraerythrocytic cycle of Plasmodium. In this work, we report that this synchrony, observed in the majority of the parasites species, could be used as a way to evade the immune system, assuring the continuity of the infection. When we disrupt this synchrony with luzindole, a melatonin antagonist, we observe that a suboptimal dose of the antimalarial chloroquine increases the survival of the infected mice. We also report that P. berghei, rodent parasite that possess and unsynchronized infection, cant perceive the hormone. Unlike what is observed in species that have a synchronous infection, melatonin fail to induce intracellular calcium increase or promote cell cycle synchronization in vitro. Here we also report the construction of knockout vector for Plasmodium, to be used to investigate the functions of the target genes by phenotype analysis.
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Visualising Plasmodium falciparum functional genomic data in MaGnET : malaria genome exploration toolSharman, Joanna Louise January 2009 (has links)
Malaria affects the lives of 500 million people around the world each year. The disease is caused by protozoan parasites of the genus Plasmodium, whose ability to evade the immune system and quickly evolve resistance to drugs poses a major challenge for disease control. The results of several Plasmodium genome sequencing projects have revealed how little is known about the function of their genes (over half of the approximately 5400 genes in Plasmodium falciparum, the most deadly human parasite, are annotated as hypothetical ). Recently, several large-scale studies have attempted to shed light on the processes in which genes are involved; for example, the use of DNA microarrays to profile the parasite s gene expression. With the emergence of varied types of functional genomic data comes a need for effective tools that allow biologists (and bioinformaticians) to explore these data. The goal of exploration/browsing-style analyses will typically be to derive clues towards the function of thus far uncharacterised gene products, and to formulate experimentally testable hypotheses. Graphic interfaces to individual data sets are obviously beneficial in this endeavour. However, effective visual data exploration requires also that interfaces to different functional genomic data are integrated and that the user can carry forward a selected group of genes (not merely one at a time) across a variety of data sets. Non-expert users especially benefit from workbenchlike tools offering access to the data in this way. Still, only very few of the contemporary publicly available software have implemented such functionality. This work introduces a novel software tool for the integrated visualisation of functional genomic data relating to P. falciparum: the Malaria Genome Exploration Tool (MaGnET). MaGnET consists of a light-weight Java program for effective visualisation linked to a MySQL database for data storage. In order to maximise accessibility, the program is publicly available over the World Wide Web (http://www.malariagenomeexplorer.org/). MaGnET incorporates a Genome Viewer for visualising the location of genomic features, a Protein-Protein Interaction Viewer for visualising networks of experimentally determined interactions and an Expression Data Viewer for displaying mRNA and protein expression data. Complex database queries can easily be constructed in the Data Analysis Viewer. An advantage over most other tools is that all sections are fully integrated, allowing users to carry selected groups of genes across different datasets. Furthermore, MaGnET provides useful advanced visualisation features, including mapping of expression data onto genomic location or protein-protein interaction network. The inclusion of available third-party Java software has expanded the visualisation capability of MaGnET; for example, the Jmol viewer has been incorporated for viewing 3-D protein structures. An effort has been made to only include data in MaGnET that is at least of reasonable quality. The MaGnET database collates experimental data from various public Plasmodium resources (e.g. PlasmoDB) and from published functional genomic studies, such as DNA microarrays. In addition, through careful filtering and labelling we have been able to include some predicted annotation that has not been experimentally confirmed, such as Gene Ontology and InterPro functional assignments and modelled protein structures. The application of MaGnET to malaria biology is demonstrated through a series of small studies. Initial examples show how MaGnET can be used to effectively demonstrate results from previously published analyses. This is followed up by using MaGnET to make a set of predictions about the possible functions of selected uncharacterised genes and suggesting follow-up experiments.
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