Medicine and Health Sciences Commons^™

Geospatial Modelling Of Lymphatic Filariasis And Malaria Co-Endemicity In Nigeria, Obiora A Eneanya, Lisa J Reimer, Peter U Fischer, Gary J Weil

2020-Current year OA Pubs

BACKGROUND: Lymphatic filariasis (LF) and malaria are important vector-borne diseases that are co-endemic throughout Nigeria. These infections are transmitted by the same mosquito vector species in Nigeria and their transmission is similarly influenced by climate and sociodemographic factors. The goal of this study was to assess the relationship between the geospatial distribution of both infections in Nigeria to better coordinate interventions.

METHODS: We used national survey data for malaria from the Demographic and Health Survey dataset and site-level LF mapping data from the Nigeria Lymphatic Filariasis Control Programme together with a suite of predictive climate and sociodemographic factors to build …

Activation Of The Plasmodium Egress Effector Subtilisin-Like Protease 1 Is Mediated By Plasmepsin X Destruction Of The Prodomain, Sumit Mukherjee, Armiyaw S. Nasamu, Kelly C. Rubiano, Daniel E. Goldberg

2020-Current year OA Pubs

Following each round of replication, daughter merozoites of the malaria parasite Plasmodium falciparum escape (egress) from the infected host red blood cell (RBC) by rupturing the parasitophorous vacuole membrane (PVM) and the RBC membrane (RBCM). A proteolytic cascade orchestrated by a parasite serine protease, subtilisin-like protease 1 (SUB1), regulates the membrane breakdown. SUB1 activation involves primary autoprocessing of the 82-kDa zymogen to a 54-kDa (p54) intermediate that remains bound to its inhibitory propiece (p31) postcleavage. A second processing step converts p54 to the terminal 47-kDa (p47) form of SUB1. Although the aspartic protease plasmepsin X (PM X) has been implicated …

Apolipoprotein E Genetic Variation, Atherogenic Index And Cardiovascular Disease Risk Assessment In An African Population: An Analysis Of Hiv And Malaria Patients In Ghana, Nicholas Ekow Thomford, Akwasi Anyanful, Richmond Owusu Ateko, Dee Blackhurst, Robert Peter Biney, Dennis Boadi, Samuel Badu Nyarko, Martins Ekor, George Boateng Kyei

2020-Current year OA Pubs

BACKGROUND: Apolipoprotein E is involved in lipid transport and clearance of lipoprotein through low-density lipoprotein receptors (LDLR). ApoE variation has been linked to cardiovascular disease (CVD) risk. There are 3 isoforms of ApoE which originate from two non-synonymous single nucleotide polymorphisms denoted as ε2, ε3 and ε4. The ε2 isoform is implicated in higher levels of atherogenic lipoprotein with the ε4 isoform causing LDLR downregulation. This leads to variable effects and differential CVD risk. Malaria and HIV are life-threatening diseases affecting several countries globally especially in sub-Saharan Africa. Parasite and viral activities have been implicated in lipid dysregulation leading to …

Mahpic Malaria Systems Biology Data From Plasmodium Cynomolgi Sporozoite Longitudinal Infections In Macaques, Jeremy D Debarry, Xuntian Jiang, Daniel S Ory, Et Al.

2020-Current year OA Pubs

Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for …

Discovery And Characterization Of Potent, Efficacious, Orally Available Antimalarial Plasmepsin X Inhibitors And Preclinical Safety Assessment Of Ucb7362, Martin A Lowe, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Plasmepsin X (PMX) is an essential aspartyl protease controlling malaria parasite egress and invasion of erythrocytes, development of functional liver merozoites (prophylactic activity), and blocking transmission to mosquitoes, making it a potential multistage drug target. We report the optimization of an aspartyl protease binding scaffold and the discovery of potent, orally active PMX inhibitors with in vivo antimalarial efficacy. Incorporation of safety evaluation early in the characterization of PMX inhibitors precluded compounds with a long human half-life (

Prioritization Of Molecular Targets For Antimalarial Drug Discovery, Barbara Forte, Daniel E Goldberg, Eva S Istvan, Et Al

2020-Current year OA Pubs

There is a shift in antimalarial drug discovery from phenotypic screening toward target-based approaches, as more potential drug targets are being validated in

Malda, Accelerating Malaria Drug Discovery, Tuo Yang, Eva S. Istvan, Daniel E. Goldberg, Et Al.

2020-Current year OA Pubs

The Malaria Drug Accelerator (MalDA) is a consortium of 15 leading scientific laboratories. The aim of MalDA is to improve and accelerate the early antimalarial drug discovery process by identifying new, essential, druggable targets. In addition, it seeks to produce early lead inhibitors that may be advanced into drug candidates suitable for preclinical development and subsequent clinical testing in humans. By sharing resources, including expertise, knowledge, materials, and reagents, the consortium strives to eliminate the structural barriers often encountered in the drug discovery process. Here we discuss the mission of the consortium and its scientific achievements, including the identification of …

Pfmfr3: A Multidrug-Resistant Modulator In Plasmodium Falciparum, Frances Rocamora, Purva Gupta, Eva S Istvan, Madeline R Luth, Emma F Carpenter, Krittikorn Kümpornsin, Erika Sasaki, Jaeson Calla, Nimisha Mittal, Krypton Carolino, Edward Owen, Manuel Llinás, Sabine Ottilie, Daniel E Goldberg, Marcus C S Lee, Elizabeth A Winzeler

2020-Current year OA Pubs

In malaria, chemical genetics is a powerful method for assigning function to uncharacterized genes. MMV085203 and GNF-Pf-3600 are two structurally related napthoquinone phenotypic screening hits that kill both blood- and sexual-stage