154 results match your criteria: "Center for Malaria Research[Affiliation]"

Metabolite profiling of Artemisia afra and Artemisia annua extracts reveals divergent effects on Plasmodium falciparum.

Phytomedicine

January 2025

Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines (CIRM), University of Liège, CIRM Laboratoire de Pharmacognosie CHU B36 Av Hopital 1, Liege B36 4000, Belgium. Electronic address:

Background: Artemisia spp. have been used for millennia in traditional medicine to treat a variety of ailments, including malaria. Extracts of Artemisia afra and A.

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Unraveling the complexities of ApiAP2 regulation in Plasmodium falciparum.

Trends Parasitol

November 2024

Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA; Huck Institutes Center for Malaria Research, The Pennsylvania State University, University Park, PA 16802, USA; Huck Institutes Center for Eukaryotic Gene Regulation, The Pennsylvania State University, University Park, PA 16802, USA; Department of Chemistry, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address:

The regulation of gene expression in Plasmodium spp., the causative agents of malaria, relies on precise transcriptional control. Malaria parasites encode a limited repertoire of sequence-specific transcriptional regulators dominated by the apicomplexan APETALA 2 (ApiAP2) protein family.

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Dynamic control of gene expression is critical for blood stage development of malaria parasites. Here, we used multi-omic analyses to investigate transcriptional regulation by the chromatin-associated microrchidia protein, MORC, during asexual blood stage development of the human malaria parasite . We show that MORC (PF3D7_1468100) interacts with a suite of nuclear proteins, including APETALA2 (ApiAP2) transcription factors (AP2-G5, AP2-O5, AP2-I, PF3D7_0420300, PF3D7_0613800, PF3D7_1107800, and PF3D7_1239200), a DNA helicase DS60 (PF3D7_1227100), and other chromatin remodelers (CHD1 and EELM2).

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Contrasting genomic epidemiology between sympatric Plasmodium falciparum and Plasmodium vivax populations.

Nat Commun

September 2024

Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

The malaria parasites Plasmodium falciparum and Plasmodium vivax differ in key biological processes and associated clinical effects, but consequences on population-level transmission dynamics are difficult to predict. This co-endemic malaria study from Guyana details important epidemiological contrasts between the species by coupling population genomics (1396 spatiotemporally matched parasite genomes, primarily from 2020-21) with sociodemographic analysis (nationwide patient census from 2019). We describe how P.

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Article Synopsis
  • - The study focuses on chloroquine-resistant malaria in Brazil, specifically linked to illegal mining in the Roraima Yanomami Indigenous territory which increases the risk of resistant parasites.
  • - Researchers collected blood samples from patients in Boa Vista and performed genetic analysis to understand mutations associated with chloroquine resistance, finding that 98% of participants were from mining areas.
  • - The analysis revealed specific genetic mutations in the studied genes, but these mutations do not effectively predict chloroquine resistance, and there were no severe cases among the participants.
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Mosquito control, which is not always easily accomplished, is further complicated by the spread of invasive species. This is the case of , a mosquito native to East Asia, whose presence has been recorded in several European countries, including Italy. This mosquito found suitable ecological conditions in central Europe in general, and in northern Italy in particular, as shown by the ongoing expansion of its distribution.

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Development of the malaria parasite, Plasmodium falciparum, is regulated by a limited number of sequence-specific transcription factors (TFs). However, the mechanisms by which these TFs recognize genome-wide binding sites is largely unknown. To address TF specificity, we investigated the binding of two TF subsets that either bind CACACA or GTGCAC DNA sequence motifs and further characterized two additional ApiAP2 TFs, PfAP2-G and PfAP2-EXP, which bind unique DNA motifs (GTAC and TGCATGCA).

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The DEAD-box RNA helicase PfDOZI imposes opposing actions on RNA metabolism in Plasmodium falciparum.

Nat Commun

May 2024

Department of Internal Medicine, Morsani College of Medicine, University of South Florida, 3720 Spectrum Boulevard, Tampa, FL, 33612, USA.

In malaria parasites, the regulation of mRNA translation, storage and degradation during development and life-stage transitions remains largely unknown. Here, we functionally characterized the DEAD-box RNA helicase PfDOZI in P. falciparum.

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A nanochitosan-D-galactose formulation increases the accumulation of primaquine in the liver.

Antimicrob Agents Chemother

May 2024

Laboratory of Malaria Research, Oswaldo Cruz Institute (IOC/Fiocruz), Reference Center for Malaria Research, Diagnosis and Training, Rio de Janeiro, Brazil.

Primaquine is the mainstream antimalarial drug to prevent relapses. However, this drug can induce hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency. Nanostructure formulations of primaquine loaded with D-galactose were used as a strategy to target the drug to the liver and decrease the hemolytic risks.

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Development of Plasmodium-specific humoral immunity is critically dependent on CD4 Th cell responses and germinal center (GC) reactions during blood-stage Plasmodium infection. IL-21, a cytokine primarily produced by CD4 T cells, is an essential regulator of affinity maturation, isotype class-switching, B cell differentiation, and maintenance of GC reactions in response to many infection and immunization models. In models of experimental malaria, mice deficient in IL-21 or its receptor IL-21R fail to develop memory B cell populations and are not protected against secondary infection.

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Global Release of Translational Repression Across Host-to-Vector Transmission Event.

bioRxiv

March 2024

Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA 16802.

Article Synopsis
  • - The study focuses on how malaria parasites prepare for transmission by females producing and controlling mRNAs necessary for zygote infection, particularly using specific protein complexes to repress translation.
  • - Researchers conducted transcriptomics and proteomics to analyze the release of translational repression in parasites during the host-to-vector transmission, discovering nearly 200 transcripts that are activated post-fertilization, while some remain repressed.
  • - The findings highlight the spatial and compositional changes in the translational repressive complex (DOZI/CITH/ALBA) during transmission, showing that mRNA protein interactions shift from close proximity during repression to dissociation upon activation in zygotes.
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Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model.

Microbiol Spectr

March 2024

Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.

Multiple vaccines have been developed and licensed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While these vaccines reduce disease severity, they do not prevent infection. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract.

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Background: The WHO recommended the use of the RTS,S/AS01 malaria vaccine (RTS,S) based on a pilot evaluation in routine use in Ghana, Kenya, and Malawi. A longitudinal qualitative study was conducted to examine facilitators and barriers to uptake of a 4-dose RTS,S schedule.

Methods: A cohort of 198 caregivers of RTS,S-eligible children from communities where RTS,S was provided through the pilot were interviewed three times over a ≈22-month, 4-dose schedule.

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Mosquito control is of paramount importance, in particular, in light of the major environmental alterations associated with human activities, from climate change to the altered distribution of pathogens, including those transmitted by Arthropods. Here, we used the common house mosquito, Culex pipiens to test the efficacy of MosChito raft, a novel tool for mosquito larval control. MosChito raft is a floating hydrogel matrix, composed of chitosan, genipin and yeast cells, as bio-attractants, developed for the delivery of a Bacillus thuringiensis israeliensis (Bti)-based bioinsecticide to mosquito larvae.

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Our study leverages gene editing techniques in asexual blood stage parasites to profile novel mutations in mutant PfCRT, an important mediator of piperaquine resistance, which developed in Southeast Asian field isolates or in parasites cultured for long periods of time. We provide evidence that increased parasite fitness of these lines is the primary driver for the emergence of these PfCRT variants. These mutations differentially impact parasite susceptibility to piperaquine and chloroquine, highlighting the multifaceted effects of single point mutations in this transporter.

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IgE response to Aed al 13 and Aed al 14 recombinant allergens from saliva in humans.

World Allergy Organ J

November 2023

Entopar Lab, Department of Biosciences, University of Milan, Via Celoria 26, 20133, Milan, Italy.

Background: Mosquito bite is normally associated with mild allergic responses, but severe localized or systemic reactions are also possible. Reliable tools for the diagnosis of mosquito allergy are still unavailable. Here, we investigated the IgE response to 3 potential salivary allergens identified in the saliva of the tiger mosquito .

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Morphological and molecular insights into the diversity of biting midges from a heavily infested Mediterranean area.

Curr Res Parasitol Vector Borne Dis

September 2023

Department of Biosciences and Pediatric Clinical Research Center "Romeo and Enrica Invernizzi", University of Milan, Milan, 20133, Italy.

The genus Skuse (Diptera: Ceratopogonidae) are blood-sucking midges known to pester humans and domestic animals. In certain Mediterranean areas, midges occur in large numbers during summer and limit the use of recreational areas, also raising serious health and social concerns. Despite such impact, the diversity and distribution of in Maremma Regional Park (Tuscany Region, Italy), a heavily infested area, is not well known, and neither molecular nor detailed morphological studies exist.

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The "Sterile Insect Technique" (SIT), a promising method to control Aedes albopictus, the Asian tiger mosquito, is gaining increasing interest. Recently, the role of microbiota in mosquito fitness received attention, but the link between microbiota and larval diet in mass rearing programs for SIT remains largely unexplored. We characterized the microbiota of four larval instars, pupae and eggs of non-wild (NW) lab-reared Ae.

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Transmission of malaria parasites to the mosquito is mediated by sexual precursor cells, the gametocytes. Upon entering the mosquito midgut, the gametocytes egress from the enveloping erythrocyte while passing through gametogenesis. Egress follows an inside-out mode during which the membrane of the parasitophorous vacuole (PV) ruptures prior to the erythrocyte membrane.

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Background: This study aimed to evaluate the gap between guidelines and local clinical practice for diagnosis and treatment of uncomplicated and severe malaria, the patient characteristics, diagnostic approach, treatment, and compliance to standard guideline recommendations.

Methods: This was a multicentre, observational study conducted between October 2020 and March 2021 in which patients of all ages with symptoms suggestive of malaria and who visited a healthcare facility were prospectively enrolled in six countries in sub-Saharan Africa (The Democratic Republic of the Congo, Mozambique, Nigeria, Rwanda, The United Republic of Tanzania, and Zambia).

Results: Of 1001 enrolled patients, 735 (73.

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Development of microsatellite markers for the invasive mosquito Aedes koreicus.

Parasit Vectors

July 2023

Department of Biosciences and Pediatric Clinical Research Center "Romeo Ed Enrica Invernizzi", University of Milan, 20133, Milan, Italy.

Background: Aedes koreicus is a mosquito species native to East Asia which has recently invaded several countries in Europe. In Italy, this mosquito was first detected in the North-East in 2011 and is now widely distributed in the entire northern part of the country. The development of specific genetic markers, such as microsatellites, is necessary to uncover the dispersal routes of this mosquito from its native areas and, eventually, to plan future control interventions.

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Long-read genome assembly and gene model annotations for the rodent malaria parasite Plasmodium yoelii 17XNL.

J Biol Chem

July 2023

Department of Biochemistry and Molecular Biology, The Huck Center for Malaria Research, The Center for Eukaryotic Gene Regulation, Pennsylvania State University, University Park, Pennsylvania, USA. Electronic address:

Malaria causes >600 thousand fatalities each year, with most cases attributed to the human-infectious Plasmodium falciparum species. Many rodent-infectious Plasmodium species, like Plasmodium berghei and Plasmodium yoelii, have been used as model species that can expedite studies of this pathogen. P.

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The mitochondrion of is required for cellular acetyl-CoA metabolism and protein acetylation.

Proc Natl Acad Sci U S A

April 2023

Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21218.

Coenzyme A (CoA) biosynthesis is an excellent target for antimalarial intervention. While most studies have focused on the use of CoA to produce acetyl-CoA in the apicoplast and the cytosol of malaria parasites, mitochondrial acetyl-CoA production is less well understood. In the current study, we performed metabolite-labeling experiments to measure endogenous metabolites in lines with genetic deletions affecting mitochondrial dehydrogenase activity.

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Cripowellins from are known pesticidal and have potent antiplasmodial activity. To gain mechanistic insights to this class of natural products, studies to determine the timing of action of cripowellins within the asexual intraerythrocytic cycle of were performed and led to the observation that this class of natural products induced reversible cytostasis in the ring stage within the first 24 h of treatment. The transcriptional program necessary for to progress through the asexual intraerythrocytic life cycle is well characterized.

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