Intense, millisecond-duration bursts of radio waves (named fast radio bursts) have been detected from beyond the Milky Way
. Their dispersion measures-which are greater than would be expected if they ...had propagated only through the interstellar medium of the Milky Way-indicate extragalactic origins and imply contributions from the intergalactic medium and perhaps from other galaxies
. Although several theories exist regarding the sources of these fast radio bursts, their intensities, durations and temporal structures suggest coherent emission from highly magnetized plasma
. Two of these bursts have been observed to repeat
, and one repeater (FRB 121102) has been localized to the largest star-forming region of a dwarf galaxy at a cosmological redshift of 0.19 (refs.
). However, the host galaxies and distances of the hitherto non-repeating fast radio bursts are yet to be identified. Unlike repeating sources, these events must be observed with an interferometer that has sufficient spatial resolution for arcsecond localization at the time of discovery. Here we report the localization of a fast radio burst (FRB 190523) to a few-arcsecond region containing a single massive galaxy at a redshift of 0.66. This galaxy is different from the host of FRB 121102, as it is a thousand times more massive, with a specific star-formation rate (the star-formation rate divided by the mass) a hundred times smaller.
The 229 GHz (lambda 1.3 mm) radio emission from Orion-KL was mapped with up to 0".4 angular resolution with CARMA, allowing measurements of the flux densities of Source I ("SrcI") and the ...Becklin-Neugebauer Object (BN), the two most massive stars in this region. We find integrated flux densities of 310 + or - 45 mJy for SrcI and 240 + or - 35 mJy for BN. SrcI is optically thick even at 229 GHz. No trace of the H30 alpha recombination line is seen in its spectrum, although the nu sub(2) = 1, 5(5,0)-6(4,3) transition of H sub(2)O, 3450 K above the ground state, is prominent. SrcI is elongated at position angle 140degrees, as in 43 GHz images. These results are most easily reconciled with models in which the radio emission from SrcI arises via the H- free-free opacity in a T < 4500 K disk, as considered by Reid et al. By contrast, the radio spectrum of BN is consistent with p super(+)/e super(-) free-free emission from a dense (ne ~ 5 x 10 super(7) cm super(-3)), but otherwise conventional, hypercompact H II region. The source is becoming optically thin at 229 GHz, and the H30 alpha recombination line, at V sub(LSR) = 23.2 + or - 0.5 km s super(-1), is prominent in its spectrum. A Lyman continuum flux of 5 x 10 super(45) photons s super(-1), consistent with that expected from a B star, is required to maintain the ionization. Supplementary 90 GHz observations were made to measure the H41 alpha and H42 alpha recombination lines toward BN. Published 43 and 86 GHz data suggest that SrcI brightened with respect to BN over the 15 year period from 1994 to 2009.
Using CARMA, we imaged the 87 GHz SiO v = 0 J = 2-1 line toward Orion-KL with 0.''45 angular resolution. The maps indicate that radio source I drives a bipolar outflow into the surrounding molecular ...cloud along a NE-SW axis, in agreement with the model of Greenhill et al. The extended high-velocity outflow from Orion-KL appears to be a continuation of this compact outflow. High-velocity gas extends farthest along a NW-SE axis, suggesting that the outflow direction changes on timescales of a few hundred years.
The rapid growth of structural information for G-protein-coupled receptors (GPCRs) has led to a greater understanding of their structure, function, selectivity, and ligand binding. Although novel ...ligands have been identified using methods such as virtual screening, computationally driven lead optimization has been possible only in isolated cases because of challenges associated with predicting binding free energies for related compounds. Here, we provide a systematic characterization of the performance of free-energy perturbation (FEP) calculations to predict relative binding free energies of congeneric ligands binding to GPCR targets using a consistent protocol and no adjustable parameters. Using the FEP+ package, first we validated the protocol, which includes a full lipid bilayer and explicit solvent, by predicting the binding affinity for a total of 45 different ligands across four different GPCRs (adenosine A2AAR, β1 adrenergic, CXCR4 chemokine, and δ opioid receptors). Comparison with experimental binding affinity measurements revealed a highly predictive ranking correlation (average spearman ρ = 0.55) and low root-mean-square error (0.80 kcal/mol). Next, we applied FEP+ in a prospective project, where we predicted the affinity of novel, potent adenosine A2A receptor (A2AR) antagonists. Four novel compounds were synthesized and tested in a radioligand displacement assay, yielding affinity values in the nanomolar range. The affinity of two out of the four novel ligands (plus three previously reported compounds) was correctly predicted (within 1 kcal/mol), including one compound with approximately a tenfold increase in affinity compared to the starting compound. Detailed analyses of the simulations underlying the predictions provided insights into the structural basis for the two cases where the affinity was overpredicted. Taken together, these results establish a protocol for systematically applying FEP+ to GPCRs and provide guidelines for identifying potent molecules in drug discovery lead optimization projects.
Abstract
Ten years ago, the genus-level and species-level taxonomy of African pipistrelloid bats was in a state of flux. In spite of advances in the past decade, gaps in collecting from species-rich ...regions like Angola have hampered efforts to revise this group. We report on new collections of pipistrelle-like bats from the poorly sampled central highlands of Angola (1000–1500 m a.s.l.) as well as comparative material from lower-lying areas of Eswatini and South Africa. Specimens identified as Neoromicia anchietae, collected 400–700 km east of the holotype locality in the western highlands of Angola, were genetically and morphologically distinctive from N. anchietae s.l. from South Africa and Eswatini. We describe herein this latter lineage as a distinct species from low-lying areas of south-eastern Africa, distinct from N. anchietae s.s., which is therefore restricted to the central and western Angolan highlands. We also identified shallow to deep genetic divergence between different African regions in other recognized pipistrelloid species, such as conspecificity between the long-eared species Laephotis angolensis from Angola and Laephotis botswanae from northern Botswana, northern Namibia and south-western Zambia. Our phylogeny supports a recently proposed generic classification of African pipistrelloid bats.
This revised edition of Bats of Southern and Central Africa builds on the solid foundation of the first edition and supplements the original account of bat species then known to be found in Southern ...and Central Africa with an additional eight newly described species, bringing the total to 124. The chapters on evolution, biogeography, ecology and echolocation have been updated, citing dozens of recently published papers. The book covers the latest systematic and taxonomic studies, ensuring that the names and relationships of bats in this new edition reflect current scientific knowledge. The species accounts provide descriptions, measurements and diagnostic characters as well as detailed information about the distribution, habitat, roosting habits, foraging ecology and reproduction of each species. The updated species distribution maps are based on 6 100 recorded localities. A special feature of the 2010 publication was the mode of identification of families, genera and species by way of character matrices rather than the more generally used dichotomous keys. Since then these matrices have been tested in the field and, where necessary, slightly altered for this edition. New photographs fill in gaps and updated sonograms aid with bat identification in acoustic surveys. The bibliography, which now contains more than 700 entries, will be an invaluable aid to students and scientists wishing to consult original research. This newly revised edition of Bats of Southern and Central Africa builds on the solid foundation of the first edition and supplements the original account of bat species then known to be found in Southern and Central Africa with an additional eight newly described species, bringing the total to 124. The chapters on evolution, biogeography, ecology and echolocation have been updated, citing dozens of recently published papers. The book covers the latest systematic and taxonomic studies, ensuring that the names and relationships of bats in this new edition reflect current scientific knowledge. The species accounts provide descriptions, measurements and diagnostic characters as well as detailed information about the distribution, habitat, roosting habits, foraging ecology and reproduction of each species. The updated species distribution maps are based on 6 100 recorded localities. A special feature of the 2010 publication was the mode of identification of families, genera and species by way of character matrices rather than the more generally used dichotomous keys. Since then these matrices have been tested in the field and, where necessary, slightly altered for this edition. New photographs fill in gaps and updated sonograms aid with bat identification in acoustic surveys. The bibliography, which now contains more than 700 entries, will be an invaluable aid to students and scientists wishing to consult original research.
The Makgadikgadi Pans in northern Botswana are the desiccated relicts of a former major inland lake system, with fossil shorelines preserved at five distinct elevations (approximately 995 m, 945 m, ...936 m, 920 m and 912 m). These lakes persisted in the Makgadikgadi Basin, which evolved in the Okavango-Makgadikgadi Rift Zone: the south-western extension of the East African Rift System (EARS) into northern Botswana. This paper synthesizes cross-disciplinary evidence, which reveals that the antiquity of this lake complex has been widely underestimated. It presents a Regional Drainage Evolution Model that invokes tectonically initiated drainage reorganizations as the underlying control over lake evolution. Lake formation was initiated by rift-flank uplift along the Chobe Fault, across the course of the Zambezi River, which diverted the regional drainage net into the Makgadikgadi Basin. Filling of the basin initiated a major climatic feedback mechanism that locally increased rainfall and lowered evaporation rates. This progressively enhanced water input to the basin, and most likely led to overtopping of the Chobe Horst barrier during the three highest lake stands, with outflow into the Zambezi River. During this period, the hydrology of the basin would have been closely analogous to modern, shallow Lake Victoria. Fragmentation of the regional drainage network by successive river captures resulted in sequential contractions of the lake to lower elevation shorelines. In turn, resultant decreases in areas of these successive lakes modulated the magnitude of the feedback mechanism. Thus, loss of the Upper Chambeshi catchment caused the lake to drop from the 990 to the 945 m level. Severance of the former link between the Kafue and Zambezi resulted in a further drop to the 936 m shoreline. Inflow declined further after the impoundment of a major lake (Palaeo-Lake Bulozi) on the Upper Zambezi River, causing contraction to the 920 m shoreline. Continued incision of the Zambezi channel into the Chobe horst barrier ultimately terminated input from this river to the Makgadikgadi depression, causing contraction of the lake below 920 m, sustained by the Cuando and Okavango prior to final desiccation. This Regional Drainage Evolution Model contradicts previous proposals that have invoked Late Pleistocene climatic forcing to explain inferred fluctuations in lake levels. The timeframe developed for the drainage reorganizations requires that the lake was initiated by approximately 1.40 to 0.51 Ma at the most recent (Early - Mid-Pleistocene), while archaeological evidence shows that it had contracted below the 936 m shoreline before 500 ka. This contrasts with 14C and quartz luminescence dates (generally <100 ka), which require that the 945 m lake stage was extant during much of the Upper Pleistocene. The calcareous radiocarbon dates reflect multiple episodes of calcrete formation, while the young luminescence dates are ascribed to the extensive bioturbation of older Kalahari landforms.
We respond to recent criticisms of supposed “taxonomic anarchy” which is said to hamper conservation efforts. Using examples from African small mammals, we document recent increases of 13% (rodents) ...and 18% (bats) over the past three decades in the number of recognized species of Afro-Malagasy rodents and bats. By reference to a number of case studies involving Afro-Malagasy taxa (predominantly from montane habitats), and a suggested four-criterion approach to delimiting species accurately, we show that these increases are a genuine reflection of speciation in cryptic species complexes. Moreover, we show that some of these cryptic species are subject to increased extinction risks due to small population size and anthropogenic changes (habitat degradation and climate change). These changes were captured accurately in a recent Mammal Red List of South Africa, Lesotho and Swaziland, indicating that taxonomists and conservationists can work together to assess the Red List status of cryptic species based on robust taxonomic revisions.
South-central Africa is characterized by an archipelago of wetlands, which has evolved in time and space since at least the Miocene, providing refugia for animal species during Pleistocene arid ...episodes. Their importance for biodiversity in the region is reflected in the evolution of a variety of specialist mammal and bird species, adapted to exploit these wetland habitats. Populations of lions (Panthera leo) across south-central and east Africa have contrasting signatures of mitochondrial DNA haplotypes and biparental nuclear DNA in wetland and savannah habitats, respectively, pointing to the evolution of distinct habitat preferences. This explains the absence of genetic admixture of populations from the Kalahari savannah of southwest Botswana and the Okavango wetland of northern Botswana, despite separation by only 500 km. We postulate that ancestral lions were wetland specialists and that the savannah lions evolved from populations that were isolated during arid Pleistocene episodes. Expansion of grasslands and the resultant increase in herbivore populations during mesic Pleistocene climatic episodes provided the stimulus for the rapid population expansion and diversification of the highly successful savannah lion specialists. Our model has important implications for lion conservation.
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