34 research outputs found
Virus-like particles identify an HIV V1V2 Apex-1 binding neutralizing antibody that lacks a protruding loop
Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, enabl them to penetrate the HIV-1
glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01-11, using virus-like particles and conformationally stabilized Env trimers as B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2 revealed a binding mode involving side-chain to side-chain interactions that reduced the distance the antibody loop must traverse the glycan shield, facilitating V1V2
binding via a non-protruding loop. The N90-VRC38 lineage identifies a solution for V1V2apex binding that provides a more conventional B cell pathway for vaccine design
The First Post-Kepler Brightness Dips of KIC 8462852
We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in 2015 October, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1%-2.5% dips, named Elsie, Celeste, Skara Brae, and Angkor, which persist on timescales from several days to weeks. Our main results so far are as follows: (i) there are no apparent changes of the stellar spectrum or polarization during the dips and (ii) the multiband photometry of the dips shows differential reddening favoring non-gray extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale ≪1 μm, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term secular dimming, which may be caused by independent processes, or probe different regimes of a single process
Application of B cell immortalization for the isolation of antibodies and B cell clones from vaccine and infection settings
The isolation and characterization of neutralizing antibodies from infection and vaccine settings informs future vaccine design, and methodologies that streamline the isolation of antibodies and the generation of B cell clones are of great interest. Retroviral transduction to express Bcl-6 and Bcl-xL and transform primary B cells has been shown to promote long-term B cell survival and antibody secretion in vitro, and can be used to isolate antibodies from memory B cells. However, application of this methodology to B cell subsets from different tissues and B cells from chronically infected individuals has not been well characterized. Here, we characterize Bcl-6/Bcl-xL B cell immortalization across multiple tissue types and B cell subsets in healthy and HIV-1 infected individuals, as well as individuals recovering from malaria. In healthy individuals, naïve and memory B cell subsets from PBMCs and tonsil tissue transformed with similar efficiencies, and displayed similar characteristics with respect to their longevity and immunoglobulin secretion. In HIV-1-viremic individuals or in individuals with recent malaria infections, the exhausted CD27-CD21- memory B cells transformed with lower efficiency, but the transformed B cells expanded and secreted IgG with similar efficiency. Importantly, we show that this methodology can be used to isolate broadly neutralizing antibodies from HIV-infected individuals. Overall, we demonstrate that Bcl-6/Bcl-xL B cell immortalization can be used to isolate antibodies and generate B cell clones from different B cell populations, albeit with varying efficiencies
New member of the V1V2-directed CAP256-VRC26 lineage that shows increased breadth and exceptional potency.
CAPRISA, 2016.Abstract available in pdf
The First Post-Kepler Brightness Dips of KIC 8462852
We present a photometric detection of the first brightness dips of the unique variable star KIC 8462852 since the end of the Kepler space mission in 2013 May. Our regular photometric surveillance started in October 2015, and a sequence of dipping began in 2017 May continuing on through the end of 2017, when the star was no longer visible from Earth. We distinguish four main 1-2.5% dips, named "Elsie," "Celeste," "Skara Brae," and "Angkor", which persist on timescales from several days to weeks. Our main results so far are: (i) there are no apparent changes of the stellar spectrum or polarization during the dips; (ii) the multiband photometry of the dips shows differential reddening favoring non-grey extinction. Therefore, our data are inconsistent with dip models that invoke optically thick material, but rather they are in-line with predictions for an occulter consisting primarily of ordinary dust, where much of the material must be optically thin with a size scale <<1um, and may also be consistent with models invoking variations intrinsic to the stellar photosphere. Notably, our data do not place constraints on the color of the longer-term "secular" dimming, which may be caused by independent processes, or probe different regimes of a single process
Another Shipment of Six Short-Period Giant Planets from TESS
We present the discovery and characterization of six short-period, transiting
giant planets from NASA's Transiting Exoplanet Survey Satellite (TESS) --
TOI-1811 (TIC 376524552), TOI-2025 (TIC 394050135), TOI-2145 (TIC 88992642),
TOI-2152 (TIC 395393265), TOI-2154 (TIC 428787891), & TOI-2497 (TIC 97568467).
All six planets orbit bright host stars (8.9 <G< 11.8, 7.7 <K< 10.1). Using a
combination of time-series photometric and spectroscopic follow-up observations
from the TESS Follow-up Observing Program (TFOP) Working Group, we have
determined that the planets are Jovian-sized (R = 1.00-1.45 R),
have masses ranging from 0.92 to 5.35 M, and orbit F, G, and K stars
(4753 T 7360 K). We detect a significant orbital eccentricity
for the three longest-period systems in our sample: TOI-2025 b (P = 8.872 days,
= ), TOI-2145 b (P = 10.261 days, =
), and TOI-2497 b (P = 10.656 days, =
). TOI-2145 b and TOI-2497 b both orbit subgiant host
stars (3.8 g 4.0), but these planets show no sign of inflation
despite very high levels of irradiation. The lack of inflation may be explained
by the high mass of the planets; M (TOI-2145
b) and M (TOI-2497 b). These six new discoveries
contribute to the larger community effort to use {\it TESS} to create a
magnitude-complete, self-consistent sample of giant planets with
well-determined parameters for future detailed studies.Comment: 20 Pages, 6 Figures, 8 Tables, Accepted by MNRA
Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.
CAPRISA, 2017.Abstract available in pdf
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
The Science Performance of JWST as Characterized in Commissioning
This paper characterizes the actual science performance of the James Webb
Space Telescope (JWST), as determined from the six month commissioning period.
We summarize the performance of the spacecraft, telescope, science instruments,
and ground system, with an emphasis on differences from pre-launch
expectations. Commissioning has made clear that JWST is fully capable of
achieving the discoveries for which it was built. Moreover, almost across the
board, the science performance of JWST is better than expected; in most cases,
JWST will go deeper faster than expected. The telescope and instrument suite
have demonstrated the sensitivity, stability, image quality, and spectral range
that are necessary to transform our understanding of the cosmos through
observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures;
https://iopscience.iop.org/article/10.1088/1538-3873/acb29