GPCRTree: online hierarchical classification of GPCR function

Background: G protein-coupled receptors (GPCRs) play important physiological roles transducing extracellular signals into intracellular responses. Approximately 50% of all marketed drugs target a GPCR. There remains considerable interest in effectively predicting the function of a GPCR from its primary sequence. Findings: Using techniques drawn from data mining and proteochemometrics, an alignment-free approach to GPCR classification has been devised. It uses a simple representation of a protein's physical properties. GPCRTree, a publicly-available internet server, implements an algorithm that classifies GPCRs at the class, sub-family and sub-subfamily level. Conclusion: A selective top-down classifier was developed which assigns sequences within a GPCR hierarchy. Compared to other publicly available GPCR prediction servers, GPCRTree is considerably more accurate at every level of classification. The server has been available online since March 2008 at URL: http://igrid-ext.cryst.bbk.ac.uk/gpcrtree

Excavating Awareness and Power in Data Science: A Manifesto for Trustworthy Pervasive Data Research

Frequent public uproar over forms of data science that rely on information about people demonstrates the challenges of defining and demonstrating trustworthy digital data research practices. This paper reviews problems of trustworthiness in what we term pervasive data research: scholarship that relies on the rich information generated about people through digital interaction. We highlight the entwined problems of participant unawareness of such research and the relationship of pervasive data research to corporate datafication and surveillance. We suggest a way forward by drawing from the history of a different methodological approach in which researchers have struggled with trustworthy practice: ethnography. To grapple with the colonial legacy of their methods, ethnographers have developed analytic lenses and researcher practices that foreground relations of awareness and power. These lenses are inspiring but also challenging for pervasive data research, given the flattening of contexts inherent in digital data collection. We propose ways that pervasive data researchers can incorporate reflection on awareness and power within their research to support the development of trustworthy data science

Observations of cold extragalactic gas clouds at z=0.45z = 0.45 towards PKS 1610-771

We present results from MUSE observations of a 21-cm HI absorption system detected with the Australian Square Kilometre Array Pathfinder radio telescope at redshift $z = 0.4503$ towards the $z = 1.71$ quasar PKS 1610-771. We identify four galaxies (A, B, X and Y) at the same redshift as the 21-cm H I Damped Lyman-{\alpha} (DLA) absorption system, with impact parameters ranging from less than 10 kpc to almost 200 kpc from the quasar sightline. Ca II and Na I absorption is seen in the MUSE spectrum of the background QSO, with velocities coinciding with the initial HI 21-cm detection, but tracing less dense and warmer gas. This metal-line component aligns with the rotating ionised disc of galaxy B (impact parameter 18 kpc from the QSO) and appears to be co-rotating with the galaxy disc. In contrast, the 21-cm HI absorber is blueshifted relative to the galaxies nearest the absorber and has the opposite sign to the velocity field of galaxy B. Since galaxies A and B are separated by only 17 kpc on the sky and $70$ km s$^{-1}$ in velocity, it appears likely that the 21-cm detection traces extragalactic clouds of gas formed from their interaction. This system reveals that the cold 100 K neutral gas critical for star formation can be associated with complex structures beyond the galaxy disc, and is a first case study made in preparation for future large 21-cm absorption surveys like the ASKAP First Large Absorption Survey in HI.Comment: Accepted. 13 pages, 7 figure

Data-driven discovery of molecular photoswitches with multioutput Gaussian processes

Photoswitchable molecules display two or more isomeric forms that may be accessed using light. Separating the electronic absorption bands of these isomers is key to selectively addressing a specific isomer and achieving high photostationary states whilst overall red-shifting the absorption bands serves to limit material damage due to UV-exposure and increases penetration depth in photopharmacological applications. Engineering these properties into a system through synthetic design however, remains a challenge. Here, we present a data-driven discovery pipeline for molecular photoswitches underpinned by dataset curation and multitask learning with Gaussian processes. In the prediction of electronic transition wavelengths, we demonstrate that a multioutput Gaussian process (MOGP) trained using labels from four photoswitch transition wavelengths yields the strongest predictive performance relative to single-task models as well as operationally outperforming time-dependent density functional theory (TD-DFT) in terms of the wall-clock time for prediction. We validate our proposed approach experimentally by screening a library of commercially available photoswitchable molecules. Through this screen, we identified several motifs that displayed separated electronic absorption bands of their isomers, exhibited red-shifted absorptions, and are suited for information transfer and photopharmacological applications. Our curated dataset, code, as well as all models are made available at https://github.com/Ryan-Rhys/The-Photoswitch-Dataset

A successful search for intervening 21 cm HI absorption in galaxies at 0.4 < z <1.0 with the Australian Square Kilometre Array Pathfinder (ASKAP)

We have used the Australian Square Kilometre Array Pathfinder (ASKAP) radio telescope to search for intervening 21 cm neutral hydrogen (HI) absorption along the line of sight to 53 bright radio continuum sources. Our observations are sensitive to HI column densities typical of Damped Lyman Alpha absorbers (DLAs) in cool gas with an HI spin temperature below about 300-500 K. The six-dish Boolardy Engineering Test Array (BETA) and twelve-antenna Early Science array (ASKAP-12) covered a frequency range corresponding to redshift $0.4<z<1.0$ and $0.37<z<0.77$ respectively for the HI line. Fifty of the 53 radio sources observed have reliable optical redshifts, giving a total redshift path $\Delta z$ = 21.37. This was a spectroscopically-untargeted survey, with no prior assumptions about the location of the lines in redshift space. Four intervening HI lines were detected, two of them new. In each case, the estimated HI column density lies above the DLA limit for HI spin temperatures above 50-80 K, and we estimate a DLA number density at redshift $z\sim0.6$ of $n(z)=0.19\substack{+0.15 \\ -0.09}$. This value lies somewhat above the general trend of $n(z)$ with redshift seen in optical DLA studies. Although the current sample is small, it represents an important proof of concept for the much larger 21cm First Large Absorption Survey in HI (FLASH) project to be carried out with the full 36-antenna ASKAP telescope, probing a total redshift path $\Delta z\sim\,50,000$.Comment: 21 pages, 11 figures. Accepted for publication in MNRA

Navigating the trade-offs between environmental DNA and conventional field surveys for improved amphibian monitoring

The need for efficient, accurate biodiversity monitoring is growing, especially for globally imperiled taxa, such as amphibians. Environmental DNA (eDNA) analysis holds enormous potential for enhancing monitoring programs, but as this tool is increasingly adopted, it is imperative for users to understand its potential benefits and shortcomings. We conducted a comparative study to evaluate the efficacy of two eDNA methodologies (quantitative (q)PCR and metabarcoding) and conventional field sampling approaches (seining, dipnetting, and visual encounter surveys) in a system of 20 ponds containing six different amphibian species. Using an occupancy modeling framework, we estimated differences in detection sensitivity across methods, with a focus on how eDNA survey design could be further optimized. Overall, both metabarcoding and qPCR were competitive with or improved upon conventional methods. Specifically, qPCR (species-specific approach) was the most effective technique for detecting two rare species, the California tiger salamander (Ambystoma californiense) and California red-legged frog (Rana draytonii), with a detection probability of &gt;0.80 per survey. Metabarcoding (community approach) estimated amphibian diversity with comparable rates to field techniques on average, and detected an additional 41 vertebrate taxa. However, for two abundant species (western toads, Anaxyrus boreas, and Pacific chorus frogs, Pseudacris regilla), field techniques outperformed metabarcoding, especially as individuals metamorphosed. Our results indicate that eDNA approaches would be most effective when paired with visual encounter surveys to detect terrestrial life stages, and that more optimization, specifically primer choice and validation, is needed. By comparing methods across a diverse set of ponds and species, we provide guidance for future studies integrating eDNA approaches into amphibian monitoring. &nbsp;</p

A search for radio afterglows from gamma-ray bursts with the Australian Square Kilometre Array Pathfinder

We present a search for radio afterglows from long gamma-ray bursts using the Australian Square Kilometre Array Pathfinder (ASKAP). Our search used the Rapid ASKAP Continuum Survey, covering the entire celestial sphere south of declination $+41^\circ$, and three epochs of the Variables and Slow Transients Pilot Survey (Phase 1), covering $\sim 5,000$ square degrees per epoch. The observations we used from these surveys spanned a nine-month period from 2019 April 21 to 2020 January 11. We crossmatched radio sources found in these surveys with 779 well-localised (to $\leq 15''$) long gamma-ray bursts occurring after 2004 and determined whether the associations were more likely afterglow- or host-related through the analysis of optical images. In our search, we detected one radio afterglow candidate associated with GRB 171205A, a local low-luminosity gamma-ray burst with a supernova counterpart SN 2017iuk, in an ASKAP observation 511 days post-burst. We confirmed this detection with further observations of the radio afterglow using the Australia Telescope Compact Array at 859 days and 884 days post-burst. Combining this data with archival data from early-time radio observations, we showed the evolution of the radio spectral energy distribution alone could reveal clear signatures of a wind-like circumburst medium for the burst. Finally, we derived semi-analytical estimates for the microphysical shock parameters of the burst: electron power-law index $p = 2.84$, normalised wind-density parameter $A_* = 3$, fractional energy in electrons $\epsilon_{e} = 0.3$, and fractional energy in magnetic fields $\epsilon_{B} = 0.0002$.Comment: 18 pages, 7 figures; accepted for publication in MNRA

Standardized NEON organismal data for biodiversity research

Understanding patterns and drivers of species distribution and abundance, and thus biodiversity, is a core goal of ecology. Despite advances in recent decades, research into these patterns and processes is currently limited by a lack of standardized, high-quality, empirical data that span large spatial scales and long time periods. The NEON fills this gap by providing freely available observational data that are generated during robust and consistent organismal sampling of several sentinel taxonomic groups within 81 sites distributed across the United States and will be collected for at least 30 years. The breadth and scope of these data provide a unique resource for advancing biodiversity research. To maximize the potential of this opportunity, however, it is critical that NEON data be maximally accessible and easily integrated into investigators\u27 workflows and analyses. To facilitate its use for biodiversity research and synthesis, we created a workflow to process and format NEON organismal data into the ecocomDP (ecological community data design pattern) format that were available through the ecocomDP R package; we then provided the standardized data as an R data package (neonDivData). We briefly summarize sampling designs and data wrangling decisions for the major taxonomic groups included in this effort. Our workflows are open-source so the biodiversity community may: add additional taxonomic groups; modify the workflow to produce datasets appropriate for their own analytical needs; and regularly update the data packages as more observations become available. Finally, we provide two simple examples of how the standardized data may be used for biodiversity research. By providing a standardized data package, we hope to enhance the utility of NEON organismal data in advancing biodiversity research and encourage the use of the harmonized ecocomDP data design pattern for community ecology data from other ecological observatory networks

Bioengineering and Semisynthesis of an Optimized Cyclophilin Inhibitor for Treatment of Chronic Viral Infection.

Inhibition of host-encoded targets, such as the cyclophilins, provides an opportunity to generate potent high barrier to resistance antivirals for the treatment of a broad range of viral diseases. However, many host-targeted agents are natural products, which can be difficult to optimize using synthetic chemistry alone. We describe the orthogonal combination of bioengineering and semisynthetic chemistry to optimize the drug-like properties of sanglifehrin A, a known cyclophilin inhibitor of mixed nonribosomal peptide/polyketide origin, to generate the drug candidate NVP018 (formerly BC556). NVP018 is a potent inhibitor of hepatitis B virus, hepatitis C virus (HCV), and HIV-1 replication, shows minimal inhibition of major drug transporters, and has a high barrier to generation of both HCV and HIV-1 resistance

Changing use of Lizard Island over the past 4000 years and implications for understanding Indigenous offshore island use on the Great Barrier Reef

Archaeological records documenting the timing and use of northern Great Barrier Reef offshore islands by Aboriginal and Torres Strait Islander peoples throughout the Holocene are limited when compared to the central and southern extents of the region. Excavations on Lizard Island, located 33 km from Cape Flattery on the mainland, provide high resolution evidence for periodic, yet sustained offshore island use over the past 4000 years, with focused exploitation of diverse marine resources and manufacture of quartz artefacts. An increase in island use occurs from around 2250 years ago, at a time when a hiatus or reduction in offshore island occupation has been documented for other Great Barrier Reef islands, but concurrent with demographic expansion across Torres Strait to the north. Archaeological evidence from Lizard Island provides a previously undocumented occupation pattern associated with Great Barrier Reef Late Holocene island use. We suggest this trajectory of Lizard Island occupation was underwritten by its place within the Coral Sea Cultural Interaction Sphere, which may highlight its significance both locally and regionally across this vast seascape