3-Position Biaryl Endochin-like Quinolones with Enhanced Antimalarial Performance.

ELQ-300 is a potent antimalarial drug with activity against blood, liver, and vector stages of the disease. A prodrug, , exhibits reduced crystallinity and improved in vivo efficacy in preclinical testing, and currently, it is in the developmental pipeline for once-a-week dosing for oral prophylaxis against malaria. Because of the high cost of developing a new drug for human use and the high risk of drug failure, it is prudent to have a back-up plan in place.

Infant diarrheal disease in rhesus macaques impedes microbiome maturation and is linked to uncultured Campylobacter species.

Diarrheal diseases remain one of the leading causes of death for children under 5 globally, disproportionately impacting those living in low- and middle-income countries (LMIC). Campylobacter spp., a zoonotic pathogen, is one of the leading causes of food-borne infection in humans.

Growth faltering regardless of chronic diarrhea is associated with mucosal immune dysfunction and microbial dysbiosis in the gut lumen.

Despite the impact of childhood diarrhea on morbidity and mortality, our understanding of its sequelae has been significantly hampered by the lack of studies that examine samples across the entire intestinal tract. Infant rhesus macaques are naturally susceptible to human enteric pathogens and recapitulate the hallmarks of diarrheal disease such as intestinal inflammation and growth faltering. Here, we examined intestinal biopsies, lamina propria leukocytes, luminal contents, and fecal samples from healthy infants and those experiencing growth faltering with distant acute or chronic active diarrhea.

ELQ-331 as a prototype for extremely durable chemoprotection against malaria.

Background: The potential benefits of long-acting injectable chemoprotection (LAI-C) against malaria have been recently recognized, prompting a call for suitable candidate drugs to help meet this need. On the basis of its known pharmacodynamic and pharmacokinetic profiles after oral dosing, ELQ-331, a prodrug of the parasite mitochondrial electron transport inhibitor ELQ-300, was selected for study of pharmacokinetics and efficacy as LAI-C in mice.

Methods: Four trials were conducted in which mice were injected with a single intramuscular dose of ELQ-331 or other ELQ-300 prodrugs in sesame oil with 1.

Maturation of the infant rhesus macaque gut microbiome and its role in the development of diarrheal disease.

Background: Diarrhea is the second leading cause of death in children under 5 years of age. Enhanced understanding of causal pathways, pathogenesis, and sequelae of diarrhea is urgently needed. Although the gut microbiota is believed to play a role in susceptibility to diarrheal diseases, our understanding of this association remains incomplete.

Risk factor analysis may provide clues to diarrhea prevention in outdoor-housed rhesus macaques (Macaca mulatta).

Seventy-five percent of rhesus macaques at national primate research centers are housed outside. Annually, 15-39% of these animals experience diarrhea and require veterinary treatment for dehydration, electrolyte imbalance, or weight loss. An estimated 21-33% of these patients will die or be euthanized.

Effects of treadmill exercise on behavioral recovery and neural changes in the substantia nigra and striatum of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse.

Our goal was to extend our understanding of the neural changes behind motor recovery with treadmill exercise in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse. We determined the extent of dopamine (DA) terminal changes using Western immunoblotting [striatal dopamine transporter (DAT) and tyrosine hydroxylase (TH)] and alterations in the mean number of DA cells/section by immunohistochemistry and Nissl staining [TH-labeled cells and thionin-stained cells in the substantia nigra pars compacta (SN-PC)]. We measured recovery of gait performance and amount of spontaneous physical activity using the parallel rod activity chamber (PRAC).

Systematic determination of differential gene expression in the primate corpus luteum during the luteal phase of the menstrual cycle.

The molecular and cellular processes required for development, function, and regression of the primate corpus luteum (CL) are poorly defined. We hypothesized that there are dynamic changes in gene expression occurring during the CL life span, which represent proteins and pathways critical to its regulation. Therefore, a genomic approach was utilized to systematically identify differentially expressed genes in the rhesus macaque CL during the luteal phase of natural menstrual cycles.

The identification of novel ovarian proteases through the use of genomic and bioinformatic methodologies.

Proteolytic activities are essential for follicular growth, ovulation, as well as for luteal formation and regression. Using suppression subtractive hybridization (SSH), a novel mouse ovary-selective gene (termed protease serine 35, Prss35) was identified. Analysis of the mouse genome database using the Prss35 sequence led to the identification of a homologous protease (protease serine 23, Prss23).

Co-induction of activity-dependent genes in songbirds.

Song behavior in songbirds induces the expression of activity-dependent genes in brain areas involved in perceptual processing, production and learning of song. This genomic response is thought to represent a link between neuronal activation and long-term changes in song-processing circuits of the songbird brain. Here we demonstrate that Arc, an activity-regulated gene whose product has dendritic localization and is associated with synaptic plasticity, is rapidly induced by song in the brain of zebra finches.

A G protein-coupled receptor encoded by rhesus rhadinovirus is similar to ORF74 of Kaposi's sarcoma-associated herpesvirus.

Rhesus rhadinovirus (RRV) is a gamma-2 herpesvirus and is the rhesus macaque homologue of human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus. DNA sequence analysis of RRV indicates that it shares numerous open reading frames (ORFs) with HHV-8, including one (ORF74) encoding a seven-transmembrane-spanning G protein-coupled receptor (GPCR) with similarity to cellular chemokine receptors. Examination of the predicted amino acid sequence of RRV ORF74 reveals that it encodes a seven-transmembrane-spanning GPCR sharing 40.