SEWAL: an open-source platform for next-generation sequence analysis and visualization

Next-generation DNA sequencing platforms provide exciting new possibilities for in vitro genetic analysis of functional nucleic acids. However, the size of the resulting data sets presents computational and analytical challenges. We present an open-source software package that employs a locality-sensitive hashing algorithm to enumerate all unique sequences in an entire Illumina sequencing run (∼108 sequences). The algorithm results in quasilinear time processing of entire Illumina lanes (∼107 sequences) on a desktop computer in minutes. To facilitate visual analysis of sequencing data, the software produces three-dimensional scatter plots similar in concept to Sewall Wright and John Maynard Smith’s adaptive or fitness landscape. The software also contains functions that are particularly useful for doped selections such as mutation frequency analysis, information content calculation, multivariate statistical functions (including principal component analysis), sequence distance metrics, sequence searches and sequence comparisons across multiple Illumina data sets. Source code, executable files and links to sample data sets are available at http://www.sourceforge.net/projects/sewal

Induction and decay of functional complement-fixing antibodies by the RTS,S malaria vaccine in children, and a negative impact of malaria exposure

Background: Leading malaria vaccine, RTS,S, is based on the circumsporozoite protein (CSP) of sporozoites. RTS,S confers partial protection against malaria in children, but efficacy wanes relatively quickly after primary immunization. Vaccine efficacy has some association with anti-CSP IgG; however, it is unclear how these antibodies function, and how functional antibodies are induced and maintained over time. Recent studies identified antibodycomplement interactions as a potentially important immune mechanism against sporozoites. Here, we investigated whether RTS,S vaccine-induced antibodies could function by interacting with complement. Methods: Serum samples were selected from children in a phase IIb trial of RTS,S/AS02A conducted at two study sites of high and low malaria transmission intensity in Manhiça, Mozambique. Samples following primary immunization and 5-year post-immunization follow-up time points were included. Vaccine-induced antibodies were characterized by isotype, subclass, and epitope specificity, and tested for the ability to fix and activate complement. We additionally developed statistical methods to model the decay and determinants of functional antibodies after vaccination. Results: RTS,S vaccination induced anti-CSP antibodies that were mostly IgG1, with some IgG3, IgG2, and IgM. Complement-fixing antibodies were effectively induced by vaccination, and targeted the central repeat and Cterminal regions of CSP. Higher levels of complement-fixing antibodies were associated with IgG that equally recognized both the central repeat and C-terminal regions of CSP. Older age and higher malaria exposure were significantly associated with a poorer induction of functional antibodies. There was a marked decay in functional complement-fixing antibodies within months after vaccination, as well as decays in IgG subclasses and IgM. Statistical modeling suggested the decay in complement-fixing antibodies was mostly attributed to the waning of anti-CSP IgG1, and to a lesser extent IgG3. Conclusions: We demonstrate for the first time that RTS,S can induce complement-fixing antibodies in young malaria-exposed children. The short-lived nature of functional responses mirrors the declining vaccine efficacy of RTS,S over time. The negative influence of age and malaria exposure on functional antibodies has implications for understanding vaccine efficacy in different settings. These findings provide insights into the mechanisms and longevity of vaccine-induced immunity that will help inform the future development of highly efficacious and longlasting malaria vaccines

A Circumplanetary Disk around PDS70c

International audiencePDS 70 is a unique system in which two protoplanets, PDS 70 b and c, have been discovered within the dust-depleted cavity of their disk, at ~22 and 34 au, respectively, by direct imaging at infrared wavelengths. Subsequent detection of the planets in the Hα line indicates that they are still accreting material through circumplanetary disks. In this Letter, we present new Atacama Large Millimeter/submillimeter Array (ALMA) observations of the dust continuum emission at 855 μm at high angular resolution (~20 mas, 2.3 au) that aim to resolve the circumplanetary disks and constrain their dust masses. Our observations confirm the presence of a compact source of emission co-located with PDS 70 c, spatially separated from the circumstellar disk and less extended than ~1.2 au in radius, a value close to the expected truncation radius of the circumplanetary disk at a third of the Hill radius. The emission around PDS 70 c has a peak intensity of ~86 ± 16 μJy beam-1, which corresponds to a dust mass of ~0.031 M⊕ or ~0.007 M⊕, assuming that it is only constituted of 1 μm or 1 mm sized grains, respectively. We also detect extended, low surface brightness continuum emission within the cavity near PDS 70 b. We observe an optically thin inner disk within 18 au of the star with an emission that could result from small micron-sized grains transported from the outer disk through the orbits of b and c. In addition, we find that the outer disk resolves into a narrow and bright ring with a faint inner shoulder

Molecules with ALMA at Planet-forming Scales (MAPS). II. CLEAN strategies for synthesizing images of molecular line emission in protoplanetary disks

Funding: I.C. was supported by NASA through NASA Hubble Fellowship grant No. HST-HF2-51405.001-A, awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. C.W. acknowledges financial support from the University of Leeds, STFC, and UKRI (grant Nos. ST/R000549/1, ST/T000287/1, MR/T040726/1) J.D.I. acknowledges support from STFC under ST/T000287/1.The Molecules with ALMA at Planet-forming Scales Large Program (MAPS LP) surveyed the chemical structures of five protoplanetary disks across more than 40 different spectral lines at high angular resolution (0"15 and 0"30 beams for Bands 6 and 3, respectively) and sensitivity (spanning 0.3-1.3 mJy beam-1 and 0.4-1.9 mJy beam-1 for Bands 6 and 3, respectively). In this article, we describe the multistage workflow-built around the CASA tclean image deconvolution procedure-that we used to generate the core data product of the MAPS LP: the position-position-velocity image cubes for each spectral line. Owing to the expansive nature of the survey, we encountered a range of imaging challenges: some are familiar to the submillimeter protoplanetary disk community, like the need to use an accurate CLEAN mask, and others are less well known, like the incorrect default flux scaling of the CLEAN residual map first described by Jorsater & van Moorsel (the "JvM effect"). We distill lessons learned into recommended workflows for synthesizing image cubes of molecular emission. In particular, we describe how to produce image cubes with accurate fluxes via "JvM correction," a procedure that is generally applicable to any image synthesized via CLEAN deconvolution but is especially critical for low signal-to-noise ratio (S/N) emission. We further explain how we used visibility tapering to promote a common, fiducial beam size and contextualize the interpretation of S/N when detecting molecular emission from protoplanetary disks. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement.Publisher PDFPeer reviewe

Molecules with ALMA at Planet-forming Scales (MAPS). I. Program overview and highlights

Funding: I.C. was supported by NASA through the NASA Hubble Fellowship grant HST-HF2-51405.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. C.W. acknowledges financial support from the University of Leeds, Science and Technology Facilities Council of the United Kingdom (STFC), and UKRI (grant Nos. ST/R000549/1, ST/T000287/1, MR/T040726/1).Planets form and obtain their compositions in dust- and gas-rich disks around young stars, and the outcome of this process is intimately linked to the disk chemical properties. The distributions of molecules across disks regulate the elemental compositions of planets, including C/N/O/S ratios and metallicity (O/H and C/H), as well as access to water and prebiotically relevant organics. Emission from molecules also encodes information on disk ionization levels, temperature structures, kinematics, and gas surface densities, which are all key ingredients of disk evolution and planet formation models. The Molecules with ALMA at Planet-forming Scales (MAPS) ALMA Large Program was designed to expand our understanding of the chemistry of planet formation by exploring disk chemical structures down to 10 au scales. The MAPS program focuses on five disks-around IM Lup, GM Aur, AS 209, HD 163296, and MWC 480-in which dust substructures are detected and planet formation appears to be ongoing. We observed these disks in four spectral setups, which together cover ~50 lines from over 20 different species. This paper introduces the Astrophysical Journal Supplement's MAPS Special Issue by presenting an overview of the program motivation, disk sample, observational details, and calibration strategy. We also highlight key results, including discoveries of links between dust, gas, and chemical substructures, large reservoirs of nitriles and other organics in the inner disk regions, and elevated C/O ratios across most disks. We discuss how this collection of results is reshaping our view of the chemistry of planet formation.Publisher PDFPeer reviewe

A glial amino-acid transporter controls synapse strength and courtship in Drosophila

Mate choice is an evolutionarily critical decision that requires the detection of multiple sex-specific signals followed by central integration of these signals to direct appropriate behavior. The mechanisms controlling mate choice remain poorly understood. Here, we show that the glial amino-acid transporter genderblind controls whether Drosophila melanogaster males will attempt to mate with other males. Genderblind (gb) mutant males showed no alteration in heterosexual courtship or copulation, but were attracted to normally unappealing male species-specific chemosensory cues. As a result, genderblind mutant males courted and attempted to copulate with other Drosophila males. This homosexual behavior could be induced within hours using inducible RNAi, suggesting that genderblind controls nervous system function rather than its development. Consistent with this, and indicating that glial genderblind regulates ambient extracellular glutamate to suppress glutamatergic synapse strength in vivo, homosexual behavior could be turned on and off by altering glutamatergic transmission pharmacologically and/or genetically

Sensory Integration Regulating Male Courtship Behavior in Drosophila

The courtship behavior of Drosophila melanogaster serves as an excellent model system to study how complex innate behaviors are controlled by the nervous system. To understand how the underlying neural network controls this behavior, it is not sufficient to unravel its architecture, but also crucial to decipher its logic. By systematic analysis of how variations in sensory inputs alter the courtship behavior of a naïve male in the single-choice courtship paradigm, we derive a model describing the logic of the network that integrates the various sensory stimuli and elicits this complex innate behavior. This approach and the model derived from it distinguish (i) between initiation and maintenance of courtship, (ii) between courtship in daylight and in the dark, where the male uses a scanning strategy to retrieve the decamping female, and (iii) between courtship towards receptive virgin females and mature males. The last distinction demonstrates that sexual orientation of the courting male, in the absence of discriminatory visual cues, depends on the integration of gustatory and behavioral feedback inputs, but not on olfactory signals from the courted animal. The model will complement studies on the connectivity and intrinsic properties of the neurons forming the circuitry that regulates male courtship behavior

Multimodal Chemosensory Integration through the Maxillary Palp in Drosophila

Drosophila melanogaster has an olfactory organ called the maxillary palp. It is smaller and numerically simpler than the antenna, and its specific role in behavior has long been unclear. Because of its proximity to the mouthparts, I explored the possibility of a role in taste behavior. Maxillary palp was tuned to mediate odor-induced taste enhancement: a sucrose solution was more appealing when simultaneously presented with the odorant 4-methylphenol. The same result was observed with other odors that stimulate other types of olfactory receptor neuron in the maxillary palp. When an antennal olfactory receptor was genetically introduced in the maxillary palp, the fly interpreted a new odor as a sweet-enhancing smell. These results all point to taste enhancement as a function of the maxillary palp. It also opens the door for studying integration of multiple senses in a model organism

An ultrahot Neptune in the Neptune desert

About 1 out of 200 Sun-like stars has a planet with an orbital period shorter than one day: an ultrashort-period planet. All of the previously known ultrashort-period planets are either hot Jupiters, with sizes above 10 Earth radii (R⊕), or apparently rocky planets smaller than 2 R⊕. Such lack of planets of intermediate size (the ‘hot Neptune desert’) has been interpreted as the inability of low-mass planets to retain any hydrogen/helium (H/He) envelope in the face of strong stellar irradiation. Here we report the discovery of an ultrashort-period planet with a radius of 4.6 R⊕ and a mass of 29 M⊕, firmly in the hot Neptune desert. Data from the Transiting Exoplanet Survey Satellite revealed transits of the bright Sun-like star LTT 9779 every 0.79 days. The planet’s mean density is similar to that of Neptune, and according to thermal evolution models, it has a H/He-rich envelope constituting 9.0^(+2.7)_(−2.9)% of the total mass. With an equilibrium temperature around 2,000 K, it is unclear how this ‘ultrahot Neptune’ managed to retain such an envelope. Follow-up observations of the planet’s atmosphere to better understand its origin and physical nature will be facilitated by the star’s brightness (V_(mag) = 9.8)