A distinct DNA methylation signature defines pediatric pre-B cell acute lymphoblastic leukemia

Pre-B cell acute lymphoblastic leukemia (ALL) is the most prevalent childhood malignancy and remains one of the highest causes of childhood mortality. Despite this, the mechanisms leading to disease remain poorly understood. We asked if recurrent aberrant DNA methylation plays a role in childhood ALL and have defined a genome-scale DNA methylation profile associated with the ETV6-RUNX1 subtype of pediatric ALL. Archival bone marrow smears from 19 children collected at diagnosis and remission were used to derive a disease specific DNA methylation profile. The gene signature was confirmed in an independent cohort of 86 patients. A further 163 patients were analyzed for DNA methylation of a three gene signature. We found that the DNA methylation signature at diagnosis was unique from remission. Fifteen loci were sufficient to discriminate leukemia from disease-free samples and purified CD34+ cells. DNA methylation of these loci was recurrent irrespective of cytogenetic subtype of pre-B cell ALL. We show that recurrent aberrant genomic methylation is a common feature of pre-B ALL, suggesting a shared pathway for disease development. By revealing new DNA methylation markers associated with disease, this study has identified putative targets for development of novel epigenetic-based therapies

Estimating female malaria mosquito age by quantifying Y-linked genes in stored male spermatozoa

Vector control strategies are among the most effective measures to combat mosquito-borne diseases, such as malaria. These strategies work by altering the mosquito age structure through increased mortality of the older female mosquitoes that transmit pathogens. However, methods to monitor changes to mosquito age structure are currently inadequate for programmatic implementation. Female mosquitoes generally mate a single time soon after emergence and draw down spermatozoa reserves with each oviposition cycle. Here, we demonstrate that measuring spermatozoa quantity in female Anopheles mosquitoes is an effective approach to assess mosquito age. Using multiplexed qPCR targeted at male spermatozoa, we show that Y-linked genes in female mosquitoes are exclusively found in the spermatheca, the organ that houses spermatozoa, and the quantity of these gene sequences significantly declines with age. The method can accurately identify mosquitoes more than 10 days old and thus old enough to potentially transmit pathogens harbored in the salivary glands during blood feeding. Furthermore, mosquito populations that differ by 10% in daily survivorship have a high likelihood of being distinguished using modest sample sizes, making this approach scalable for assessing the efficacy of vector intervention control programs

Stellar Kinematics and Environment at z~0.8 in the LEGA-C Survey:Massive, Slow-Rotators are Built First in Overdense Environments

In this Letter, we investigate the impact of environment on integrated and spatially resolved stellar kinematics of a sample of massive, quiescent galaxies at intermediate redshift (0.6 < z < 1.0). For this analysis, we combine photometric and spectroscopic parameters from the UltraVISTA and Large Early Galaxy Astrophysics Census surveys in the COSMOS field and environmental measurements. We analyze the trends with overdensity (1+δ) on the rotational support of quiescent galaxies and find no universal trends at either fixed mass or fixed stellar velocity dispersion. This is consistent with previous studies of the local universe; rotational support of massive galaxies depends primarily on stellar mass. We highlight two populations of massive galaxies () that deviate from the average mass relation. First, the most massive galaxies in the most underdense regions ((1 + δ) ≤ 1) exhibit elevated rotational support. Similarly, at the highest masses () the range in rotational support is significant in all but the densest regions. This corresponds to an increasing slow-rotator fraction such that only galaxies in the densest environments ((1 + δ) ≥ 3.5) are primarily (90% ± 10%) slow rotators. This effect is not seen at fixed velocity dispersion, suggesting minor merging as the driving mechanism: Only in the densest regions have the most massive galaxies experienced significant minor merging, building stellar mass and diminishing rotation without significantly affecting the central stellar velocity dispersion. In the local universe, most massive galaxies are slow rotators, regardless of environment, suggesting minor merging occurs at later cosmic times (z ≲ 0.6) in all but the most dense environments

Priority use cases for antibody-detecting assays of recent malaria exposure as tools to achieve and sustain malaria elimination

Measurement of malaria specific antibody responses represents a practical and informative method for malaria control programs to assess recent exposure to infection. Technical advances in recombinant antigen production, serological screening platforms, and analytical methods have enabled the identification of several target antigens for laboratory based and point-of-contact tests. Questions remain as to how these serological assays can best be integrated into malaria surveillance activities to inform programmatic decision-making. This report synthesizes discussions from a convening at Institut Pasteur in Paris in June 2017 aimed at defining practical and informative use cases for serology applications and highlights five programmatic uses for serological assays including: documenting the absence of transmission; stratification of transmission; measuring the effect of interventions; informing a decentralized immediate response; and testing and treating P. vivax hypnozoite carriers

The DEEP2 Galaxy Redshift Survey: Design, Observations, Data Reduction, and Redshifts

We describe the design and data sample from the DEEP2 Galaxy Redshift Survey, the densest and largest precision-redshift survey of galaxies at z ~ 1 completed to date. The survey has conducted a comprehensive census of massive galaxies, their properties, environments, and large-scale structure down to absolute magnitude M_B = -20 at z ~ 1 via ~90 nights of observation on the DEIMOS spectrograph at Keck Observatory. DEEP2 covers an area of 2.8 deg^2 divided into four separate fields, observed to a limiting apparent magnitude of R_AB=24.1. Objects with z < 0.7 are rejected based on BRI photometry in three of the four DEEP2 fields, allowing galaxies with z > 0.7 to be targeted ~2.5 times more efficiently than in a purely magnitude-limited sample. Approximately sixty percent of eligible targets are chosen for spectroscopy, yielding nearly 53,000 spectra and more than 38,000 reliable redshift measurements. Most of the targets which fail to yield secure redshifts are blue objects that lie beyond z ~ 1.45. The DEIMOS 1200-line/mm grating used for the survey delivers high spectral resolution (R~6000), accurate and secure redshifts, and unique internal kinematic information. Extensive ancillary data are available in the DEEP2 fields, particularly in the Extended Groth Strip, which has evolved into one of the richest multiwavelength regions on the sky. DEEP2 surpasses other deep precision-redshift surveys at z ~ 1 in terms of galaxy numbers, redshift accuracy, sample number density, and amount of spectral information. We also provide an overview of the scientific highlights of the DEEP2 survey thus far. This paper is intended as a handbook for users of the DEEP2 Data Release 4, which includes all DEEP2 spectra and redshifts, as well as for the publicly-available DEEP2 DEIMOS data reduction pipelines. [Abridged]Comment: submitted to ApJS; data products available for download at http://deep.berkeley.edu/DR4

Rejuvenation in z~0.8 quiescent galaxies in LEGA-C

We use reconstructed star-formation histories (SFHs) of quiescent galaxies at z = 0.6 − 1 in the LEGA-C survey to identify secondary star-formation episodes that, after an initial period of quiescence, moved the galaxies back to the star-forming main sequence (blue cloud). 16 ± 3% of the z ∼ 0.8 quiescent population has experienced such rejuvenation events in the redshift range 0.7 < z < 1.5 after reaching quiescence at some earlier time. On average, these galaxies first became quiescent at z = 1.2, and those that rejuvenated, remained quiescent for ∼ 1Gyr before their secondary SF episode which lasted ∼ 0.7Gyr. The stellar mass attributed to rejuvenation is on average 10% of the galaxy stellar mass, with rare instances of an increase of more than a factor 2. Overall, rejuvenation events only contribute ∼ 2% of the total stellar mass in z ∼ 0.8 quiescent galaxies and we conclude that rejuvenation is not an important evolutionary channel when considering the growth of the red sequence. However, our results complicate the interpretation of galaxy demographics in color space: the galaxies with rejuvenation events tend to lie in the so-called ‘green valley’, yet their progenitors were quiescent at z ∼ 2