Conservation importance of limestone karst outcrops for Palaeotropical bats in a fragmented landscape

Limestone karst landscapes are important for biodiversity yet are increasingly threatened by development activities such as mining. Furthermore, karsts are often scattered and isolated by agriculture, and are rarely considered in landscape planning because of a paucity of biodiversity data. We determined the conservation significance of an isolated limestone karst outcrop for insectivorous bats by quantifying the influence of this roosting resource on local assemblage structure across a fragmented landscape in peninsular Malaysia. Using a combination of rank abundance, gradient and randomisation analyses, we demonstrate that bat assemblages at nine forest sites are structured following a spatial gradient of increasing distance from a karst roosting resource. The assemblage at our karst site was dominated by a superabundance of three cave-roosting species, two of which were also found to dominate assemblages up to 11 km away. Cave-roosting bats exhibited a significant decay in abundance related to the distance from karst, with sites closest to karst also characterised by a rarity of tree cavity/foliage-roosting species that were otherwise common. Gradient analysis revealed that differences in assemblage composition were largely associated with the distance from the karst and, to a lesser extent, forest isolation and area. Our findings suggest that isolated karst outcrops can serve as important population reservoirs for cave-roosting bats, which subsidise diversity levels in forest fragments that might otherwise be expected to decline over time. While conservation efforts need to focus on maintaining large areas of connected forest, landscape management needs to ensure protection of karsts as point resources for cave-roosting bats

High-throughput screening identifies small molecule inhibitors of thioesterase superfamily member 1: Implications for the management of non-alcoholic fatty liver disease

Objective: Thioesterase superfamily member 1 (Them1) is a long chain acyl-CoA thioesterase comprising two N-terminal HotDog fold enzymatic domains linked to a C-terminal lipid-sensing steroidogenic acute regulatory transfer-related (START) domain, which allosterically modulates enzymatic activity. Them1 is highly expressed in thermogenic adipose tissue, where it functions to suppress energy expenditure by limiting rates of fatty acid oxidation, and is induced markedly in liver in response to high fat feeding, where it suppresses fatty acid oxidation and promotes glucose production. Them1−/− mice are protected against non-alcoholic fatty liver disease (NAFLD), suggesting Them1 as a therapeutic target. Methods: A high-throughput small molecule screen was performed to identify promising inhibitors targeting the fatty acyl-CoA thioesterase activity of purified recombinant Them1.Counter screening was used to determine specificity for Them1 relative to other acyl-CoA thioesterase isoforms. Inhibitor binding and enzyme inhibition were quantified by biophysical and biochemical approaches, respectively. Following structure-based optimization, lead compounds were tested in cell culture. Results: Two lead allosteric inhibitors were identified that selectively inhibited Them1 by binding the START domain. In mouse brown adipocytes, these inhibitors promoted fatty acid oxidation, as evidenced by increased oxygen consumption rates. In mouse hepatocytes, they promoted fatty acid oxidation, but also reduced glucose production. Conclusion: Them1 inhibitors could prove attractive for the pharmacologic management of NAFLD