Genetic assessment of captive breeding program of Indian Pangolin: implications for conservation and management.

BACKGROUND: Captive breeding programs play a vital role in conservation of threatened species, necessitating an understanding of genetic diversity among captive individuals to ensure long-term genetic viability, appropriate mate selection, and successful reintroduction to native habitats. METHODS AND RESULTS: We did not observe any recent genetic bottleneck, and population showed moderate genetic diversity. The estimated effective population size, representing individuals capable of contributing genetically to future generations, was estimated as 18.6 individuals (11.4-35.1 at 95% CI). Based on the genetic make-up and allelic diversity, we found seventeen pangolins (11 females and 6 males) were genetically unrelated and relatively more potent than others. CONCLUSION: In this study, we evaluated the captive breeding program of the Indian pangolin population at the Pangolin Conservation Breeding Centre in Nandankanan Zoological Park, Bhubaneswar, Odisha. We highlight the significance of genetic monitoring within the captive population of Indian pangolin for preserving genetic diversity and ensuring the long-term survival of the species. We established the genetic profiles of all 29 pangolins and identified 17 pangolins to be prioritized for enhanced breeding and future zoo exchange programs. We appreciate the zoo authorities for promoting genetic assessment of pangolin for better and more effective monitoring of the captive breeding of the endangered Indian pangolin.

Barriers and corridors: Assessment of gene flow and movement among red panda populations in eastern Himalayas.

Landscape features can impede dispersal, gene flow, and population demography, resulting in the formation of several meta-populations within a continuous landscape. Understanding a species' ability to overcome these barriers is critical for predicting genetic connectivity and population persistence, and implementing effective conservation strategies. In the present study, we conducted a fine-scale spatial genetic analysis to understand the contemporary gene flow within red panda populations in the Eastern Himalayas. Employing geometric aspects of reserve design, we delineated the critical core habitats for red pandas, which comprise 14.5 % of the landscape (12,189.75 Km2), with only a mere 443 Km2 falling within the protected areas. We identified corridors among the core habitats, which may be vital for the species' long-term genetic viability. Furthermore, we identified substantial landscape barriers, including Sela Pass in the western region, Siang river in the central region, and the Dibang river, Lohit river, along with Dihang, Dipher, and Kumjawng passes in the eastern region, which hinder gene flow. We suggest managing red panda populations through the creation of Community Conservation Reserves in the identified core habitats, following landscape-level management planning based on the core principles of geometric reserve design. This includes a specific emphasis on identified core habitats of red panda (CH-RP 5 and CH-RP 8) to facilitate corridors and implement meta-population dynamics. We propose the development of a comprehensive, long-term conservation and management plan for red pandas in the transboundary landscape, covering China, Nepal, and Bhutan.

Development of Brain Penetrant Pyridazine Pantothenate Kinase Activators.

Conversion of pantothenate to phosphopantothenate in humans is the first dedicated step in the coenzyme A (CoA) biosynthesis pathway and is mediated by four isoforms of pantothenate kinase. These enzymes are allosterically regulated by acyl-CoA levels, which control the rate of CoA biosynthesis. Small molecule activators of the PANK enzymes that overcome feedback suppression increase CoA levels in cultured cells and animals and have shown great potential for the treatment of pantothenate kinase-associated neurodegeneration and propionic acidemias. In this study, we detail the further optimization of PANK pyridazine activators using structure-guided design and focus on the cellular CoA activation potential, metabolic stability, and solubility as the primary drivers of the structure-activity relationship. These studies led to the prioritization of three late-stage preclinical lead PANK modulators with improved pharmacokinetic profiles and the ability to substantially increase brain CoA levels. Compound 22 (BBP-671) eventually advanced into clinical testing for the treatment of PKAN and propionic acidemia.