University of Georgia
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Category: publications

Aminoalkoxycarbonyloxymethyl Ether Prodrugs with a pH-Triggered Release Mechanism: A Case Study Improving the Solubility, Bioavailability, and Efficacy of Antimalarial 4(1 H)-Quinolones with Single Dose Cures

Donna Huber on May 12, 2021

Preclinical and clinical development of numerous small molecules is prevented by their poor aqueous solubility, limited absorption, and oral bioavailability. Herein, we disclose a general prodrug approach that converts promising lead compounds into aminoalkoxycarbonyloxymethyl (amino AOCOM) ether-substituted analogues that display significantly improved aqueous solubility and enhanced oral bioavailability, restoring key requirements typical for drug candidate …

Toll9 from Bombyx mori functions as a pattern recognition receptor that shares features with Toll-like receptor 4 from mammals

Donna Huber on May 10, 2021

Toll/Toll-like receptors (TLRs) are key regulators of the innate immune system in both invertebrates and vertebrates. However, while mammalian TLRs directly recognize pathogen-associated molecular patterns, the insect Toll pathway is thought to be primarily activated by binding Spätzle cytokines that are processed from inactive precursors in response to microbial infection. Phylogenetic and structural data generated …

Lacto-N-fucopentaose-III (LNFPIII) ameliorates acute aberrations in hippocampal synaptic transmission in a Gulf War Illness animal model

Donna Huber on May 4, 2021

Approximately one-third of Persian Gulf War veterans are afflicted by Gulf War Illness (GWI), a chronic multisymptom condition that fundamentally presents with cognitive deficits (i.e., learning and memory impairments) and neuroimmune dysfunction (i.e., inflammation). Factors associated with GWI include overexposures to neurotoxic pesticides and nerve agent prophylactics such as permethrin (PM) and pyridostigmine bromide (PB), …

A novel fragmented mitochondrial genome in the protist pathogen Toxoplasma gondii and related tissue coccidia

Donna Huber on April 27, 2021

Mitochondrial genome content and structure vary widely across the eukaryotic tree of life, with protists displaying extreme examples. Apicomplexan and dinoflagellate protists have evolved highly reduced mitochondrial genome sequences, mtDNA, consisting of only three cytochrome genes and fragmented rRNA genes. Here, we report the independent evolution of fragmented cytochrome genes in Toxoplasma and related tissue coccidia and …

Baseline Mapping of Neglected Tropical Diseases in Africa: The Accelerated WHO/AFRO Mapping Project

Donna Huber on April 26, 2021

Mapping is a prerequisite for effective implementation of interventions against neglected tropical diseases (NTDs). Before the accelerated WHO/AFRO NTD Mapping Project was initiated in 2014, mapping efforts in many countries were frequently carried out in an ad hoc and nonstandardized fashion. In 2013, there were at least 2,200 different districts (of the 4,851 districts in …

Some conditions apply: Systems for studying Plasmodium falciparum protein function

Donna Huber on April 22, 2021

Fig 1. Conditional protein knockdown used throughout the Plasmodium falciparum life cycle. Malaria, caused by infection with Plasmodium parasites, remains a significant global health concern. For decades, genetic intractability and limited tools hindered our ability to study essential proteins and pathways in Plasmodium falciparum, the parasite associated with the most severe malaria cases. However, recent …

Casein kinase TbCK1.2 regulates division of kinetoplast DNA, and movement of basal bodies in the African trypanosome

Donna Huber on April 16, 2021

The single mitochondrial nucleoid (kinetoplast) of Trypanosoma brucei is found proximal to a basal body (mature (mBB)/probasal body (pBB) pair). Kinetoplast inheritance requires synthesis of, and scission of kinetoplast DNA (kDNA) generating two kinetoplasts that segregate with basal bodies into daughter cells. Molecular details of kinetoplast scission and the extent to which basal body separation …

Survival of Salmonella and Shiga Toxin-producing Escherichia coli and Changes in Indigenous Microbiota During Fermentation of Kombucha Made from Home-brewing Kits

Donna Huber on April 14, 2021

Survival and growth of Salmonella and Shiga toxin-producing Escherichia coli (STEC) in kombucha prepared from four brands of commercially available kombucha kits intended for use by home brewers were investigated. Changes in microbiota responsible for fermentation were also determined. An initial population of Salmonella (6.77 log CFU/mL) decreased to below the detection limit (0.30 log …

Riboflavin instability is a key factor underlying the requirement of a gut microbiota for mosquito development

Donna Huber on April 9, 2021

We previously determined that several diets used to rear Aedes aegypti and other mosquito species support the development of larvae with a gut microbiota but do not support the development of axenic larvae. In contrast, axenic larvae have been shown to develop when fed other diets. To understand the mechanisms underlying this dichotomy, we developed a defined …