Camera Traps Uncover the Behavioral Ecology of an Endemic, Cryptic Monkey Species in the Congo Basin.

Guenons are the most diverse clade of African primates, and many species living within the core of the Congo Basin rainforest are still understudied. The recently described guenon species, Cercopithecus lomamiensis, known as lesula, is a cryptic, semi-terrestrial species endemic to the central Congo Basin in the Democratic Republic of the Congo. The recent IUCN Red List Assessment recognizes lesula's risk of extinction in the wild as Vulnerable. The objective of our study was to use camera traps to expand knowledge on the behavioral ecology of lesula. We conducted three systematic, terrestrial camera trap (CT) surveys within Lomami National Park and buffer zone (Okulu: 2013; Losekola: 2014; E15: 2015). We accumulated 598 independent events of lesula over 5960 CT days from 92 CTs. Typical of Cercopithecus species, camera trap videos reveal that lesula has a diurnal activity pattern, birth seasonality, a group size of up to 32 individuals, and social organization with female philopatry and male dispersal. Results also suggest that lesula are highly terrestrial, distinguishing them from other Cercopithecus species, which are mostly arboreal. Our study provides new information about the behavioral ecology of this little-studied primate, generating species-specific knowledge of a threatened species for successful conservation planning.

Structurally Diverse Mitochondrial Branched Chain Aminotransferase (BCATm) Leads with Varying Binding Modes Identified by Fragment Screening.

Inhibitors of mitochondrial branched chain aminotransferase (BCATm), identified using fragment screening, are described. This was carried out using a combination of STD-NMR, thermal melt (Tm), and biochemical assays to identify compounds that bound to BCATm, which were subsequently progressed to X-ray crystallography, where a number of exemplars showed significant diversity in their binding modes. The hits identified were supplemented by searching and screening of additional analogues, which enabled the gathering of further X-ray data where the original hits had not produced liganded structures. The fragment hits were optimized using structure-based design, with some transfer of information between series, which enabled the identification of ligand efficient lead molecules with micromolar levels of inhibition, cellular activity, and good solubility.

The Discovery of in Vivo Active Mitochondrial Branched-Chain Aminotransferase (BCATm) Inhibitors by Hybridizing Fragment and HTS Hits.

The hybridization of hits, identified by complementary fragment and high throughput screens, enabled the discovery of the first series of potent inhibitors of mitochondrial branched-chain aminotransferase (BCATm) based on a 2-benzylamino-pyrazolo[1,5-a]pyrimidinone-3-carbonitrile template. Structure-guided growth enabled rapid optimization of potency with maintenance of ligand efficiency, while the focus on physicochemical properties delivered compounds with excellent pharmacokinetic exposure that enabled a proof of concept experiment in mice. Oral administration of 2-((4-chloro-2,6-difluorobenzyl)amino)-7-oxo-5-propyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile 61 significantly raised the circulating levels of the branched-chain amino acids leucine, isoleucine, and valine in this acute study.