Abstract
The Alliance of Genome Resources (Alliance) is a consortium of the major model organism databases and the Gene Ontology that is guided by the vision of facilitating exploration of related ...genes in human and well-studied model organisms by providing a highly integrated and comprehensive platform that enables researchers to leverage the extensive body of genetic and genomic studies in these organisms. Initiated in 2016, the Alliance is building a central portal (www.alliancegenome.org) for access to data for the primary model organisms along with gene ontology data and human data. All data types represented in the Alliance portal (e.g. genomic data and phenotype descriptions) have common data models and workflows for curation. All data are open and freely available via a variety of mechanisms. Long-term plans for the Alliance project include a focus on coverage of additional model organisms including those without dedicated curation communities, and the inclusion of new data types with a particular focus on providing data and tools for the non-model-organism researcher that support enhanced discovery about human health and disease. Here we review current progress and present immediate plans for this new bioinformatics resource.
Many problems in contemporary astrophysics-from understanding the formation of black holes to untangling the chemical evolution of galaxies-rely on knowledge about binary stars. This, in turn, ...depends on the discovery and characterization of binary companions for large numbers of different kinds of stars in different chemical and dynamical environments. Current stellar spectroscopic surveys observe hundreds of thousands to millions of stars with (typically) few observational epochs, which allows for binary discovery but makes orbital characterization challenging. We use a custom Monte Carlo sampler (The Joker) to perform discovery and characterization of binary systems through radial velocities, in the regime of sparse, noisy, and poorly sampled multi-epoch data. We use it to generate posterior samplings in Keplerian parameters for 232,495 sources released in APOGEE Data Release 16. Our final catalog contains 19,635 high-confidence close-binary (P few years, a few ) systems that show interesting relationships between binary occurrence rate and location in the color-magnitude diagram. We find notable faint companions at high masses (black hole candidates), at low masses (substellar candidates), and at very close separations (mass-transfer candidates). We also use the posterior samplings in a (toy) hierarchical inference to measure the long-period binary-star eccentricity distribution. We release the full set of posterior samplings for the entire parent sample of 232,495 stars. This set of samplings involves no heuristic "discovery" threshold and therefore can be used for myriad statistical purposes, including hierarchical inferences about binary-star populations and subthreshold searches.
Transmission blocking vaccines targeting the sexual-stages of the malaria parasite could play a major role to achieve elimination and eradication of malaria. The
Pfs25 protein (Pfs25) is the most ...clinically advanced candidate sexual-stage antigen. IMX313, a complement inhibitor C4b-binding protein that forms heptamers with the antigen fused to it, improve antibody responses. This is the first time that viral vectors have been used to induce antibodies in humans against an antigen that is expressed only in the mosquito vector.
Clinical trial looking at safety and immunogenicity of two recombinant viral vectored vaccines encoding Pfs25-IMX313 in healthy malaria-naive adults. Replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding Pfs25-IMX313, were delivered by the intramuscular route in a heterologous prime-boost regimen using an 8-week interval. Safety data and samples for immunogenicity assays were taken at various time-points.
The reactogenicity of the vaccines was similar to that seen in previous trials using the same viral vectors encoding other antigens. The vaccines were immunogenic and induced both antibody and T cell responses against Pfs25, but significant transmission reducing activity (TRA) was not observed in most volunteers by standard membrane feeding assay.
Both vaccines were well tolerated and demonstrated a favorable safety profile in malaria-naive adults. However, the transmission reducing activity of the antibodies generated were weak, suggesting the need for an alternative vaccine formulation.
Clinicaltrials.gov NCT02532049.
Despite the tangible progress in psychological and cognitive sciences over the last several years, these disciplines still trail other more mature sciences in identifying the most important questions ...that need to be solved. Reaching such consensus could lead to greater synergy across different laboratories, faster progress, and increased focus on solving important problems rather than pursuing isolated, niche efforts. Here, 26 researchers from the field of visual metacognition reached consensus on four long-term and two medium-term common goals. We describe the process that we followed, the goals themselves, and our plans for accomplishing these goals. If this effort proves successful within the next few years, such consensus building around common goals could be adopted more widely in psychological science.
The neocortex is disproportionately expanded in human compared with mouse
, both in its total volume relative to subcortical structures and in the proportion occupied by supragranular layers composed ...of neurons that selectively make connections within the neocortex and with other telencephalic structures. Single-cell transcriptomic analyses of human and mouse neocortex show an increased diversity of glutamatergic neuron types in supragranular layers in human neocortex and pronounced gradients as a function of cortical depth
. Here, to probe the functional and anatomical correlates of this transcriptomic diversity, we developed a robust platform combining patch clamp recording, biocytin staining and single-cell RNA-sequencing (Patch-seq) to examine neurosurgically resected human tissues. We demonstrate a strong correspondence between morphological, physiological and transcriptomic phenotypes of five human glutamatergic supragranular neuron types. These were enriched in but not restricted to layers, with one type varying continuously in all phenotypes across layers 2 and 3. The deep portion of layer 3 contained highly distinctive cell types, two of which express a neurofilament protein that labels long-range projection neurons in primates that are selectively depleted in Alzheimer's disease
. Together, these results demonstrate the explanatory power of transcriptomic cell-type classification, provide a structural underpinning for increased complexity of cortical function in humans, and implicate discrete transcriptomic neuron types as selectively vulnerable in disease.
Exoplanet transit and Doppler surveys discover many binary stars during their operation that can be used to conduct a variety of ancillary science. Specifically, eclipsing binary stars can be used to ...study the stellar mass-radius relationship and to test predictions of theoretical stellar evolution models. By cross-referencing 24 binary stars found in the MARVELS Pilot Project with SuperWASP photometry, we find two new eclipsing binaries, TYC 0272-00458-1 and TYC 1422-01328-1, which we use as case studies to develop a general approach to eclipsing binaries in survey data. TYC 0272-00458-1 is a single-lined spectroscopic binary for which we calculate a mass of the secondary and radii for both components using reasonable constraints on the primary mass through several different techniques. For a primary mass of M_1 = 0.92 +/- 0.1 M_solar, we find M_2 = 0.610 +/- 0.036 M_solar, R_1 = 0.932 +/- 0.076 R_solar and R_2 = 0.559 +/- 0.102 R_solar, and find that both stars have masses and radii consistent with model predictions. TYC 1422-01328-1 is a triple-component system for which we can directly measure the masses and radii of the eclipsing pair. We find that the eclipsing pair consists of an evolved primary star (M_1 = 1.163 +/- 0.034 M_solar, R_1 = 2.063 +/- 0.058 R_solar) and a G-type dwarf secondary (M_2 = 0.905 +/- 0.067 M_solar, R_2 = 0.887 +/- 0.037 R_solar). We provide the framework necessary to apply this analysis to much larger datasets.
ABSTRACT In its three years of operation, the Sloan Digital Sky Survey Apache Point Observatory Galactic Evolution Experiment (APOGEE-1) observed >14,000 stars with enough epochs over a sufficient ...temporal baseline for the fitting of Keplerian orbits. We present the custom orbit-fitting pipeline used to create this catalog, which includes novel quality metrics that account for the phase and velocity coverage of a fitted Keplerian orbit. With a typical radial velocity precision of ∼100-200 m s−1, APOGEE can probe systems with small separation companions down to a few Jupiter masses. Here we present initial results from a catalog of 382 of the most compelling stellar and substellar companion candidates detected by APOGEE, which orbit a variety of host stars in diverse Galactic environments. Of these, 376 have no previously known small separation companion. The distribution of companion candidates in this catalog shows evidence for an extremely truncated brown dwarf (BD) desert with a paucity of BD companions only for systems with 0.1-0.2 AU, with no indication of a desert at larger orbital separation. We propose a few potential explanations of this result, some which invoke this catalog's many small separation companion candidates found orbiting evolved stars. Furthermore, 16 BD and planet candidates have been identified around metal-poor (Fe/H < −0.5) stars in this catalog, which may challenge the core accretion model for companions . Finally, we find all types of companions are ubiquitous throughout the Galactic disk with candidate planetary-mass and BD companions to distances of ∼6 and ∼16 kpc, respectively.
Abstract
APOGEE spectra offer ≲1 km s
−1
precision in the measurement of stellar radial velocities. This holds even when multiple stars are captured in the same spectrum, as happens most commonly ...with double-lined spectroscopic binaries (SB2s), although random line-of-sight alignments of unrelated stars can also occur. We develop a code that autonomously identifies SB2s and higher order multiples in the APOGEE spectra, resulting in 7273 candidate SB2s, 813 SB3s, and 19 SB4s. We estimate the mass ratios of binaries, and for a subset of these systems with a sufficient number of measurements we perform a complete orbital fit, confirming that most systems with periods of <10 days have circularized. Overall, we find an SB2 fraction (
F
SB2
) ∼ 3% among main-sequence dwarfs, and that there is not a significant trend in
F
SB2
with temperature of a star. We are also able to recover a higher
F
SB2
in sources with lower metallicity, however there are some observational biases. We also examine light curves from TESS to determine which of these spectroscopic binaries are also eclipsing. Such systems, particularly those that are also pre- and post-main sequence, are good candidates for a follow-up analysis to determine their masses and temperatures.
is an opportunistic fungal pathogen responsible for mucosal candidiasis and systemic candidemia in humans. Often, these infections are associated with the formation of drug-resistant biofilms on the ...surfaces of tissues or medical devices. Increased incidence of
resistance to current antifungals has heightened the need for new strategies to prevent or eliminate biofilm-related fungal infections. In prior studies, we designed 14-helical β-peptides to mimic the structural properties of natural antimicrobial α-peptides (AMPs) in an effort to develop active and selective antifungal compounds. These amphiphilic, cationic, helical β-peptides exhibited antifungal activity against planktonic
cells and inhibited biofilm formation
and
Recent studies have suggested the use of antivirulence agents in combination with antifungals. In this study, we investigated the use of compounds that target
polymorphism, such as 1-dodecanol, isoamyl alcohol, and farnesol, to attempt to improve β-peptide efficacy for preventing
biofilms. Isoamyl alcohol, which prevents hyphal formation, reduced the minimum biofilm prevention concentrations (MBPCs) of β-peptides by up to 128-fold. Combinations of isoamyl alcohol and antifungal β-peptides resulted in less than 10% hemolysis at the antifungal MBPCs. Overall, our results suggest potential benefits of combination therapies comprised of morphogenesis modulators and antifungal AMP peptidomimetics for preventing
biofilm formation.
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