Molecular targets of glucocorticoids that elucidate their therapeutic efficacy in aggressive lymphomas.

Glucocorticoids have been used for decades to treat lymphomas without an established mechanism of action. Using functional genomic, proteomic, and chemical screens, we discover that glucocorticoids inhibit oncogenic signaling by the B cell receptor (BCR), a recurrent feature of aggressive B cell malignancies, including diffuse large B cell lymphoma and Burkitt lymphoma. Glucocorticoids induce the glucocorticoid receptor (GR) to directly transactivate genes encoding negative regulators of BCR stability (LAPTM5; KLHL14) and the PI3 kinase pathway (INPP5D; DDIT4).

Molecular Determinants of Sensitivity to Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma.

Polatuzumab vedotin (Pola-V) is an antibody-drug conjugate directed to the CD79B subunit of the B-cell receptor (BCR). When combined with conventional immunochemotherapy, Pola-V improves outcomes in diffuse large B-cell lymphoma (DLBCL). To identify determinants of Pola-V sensitivity, we used CRISPR-Cas9 screening for genes that modulated Pola-V toxicity for lymphomas or the surface expression of its target, CD79B.

Targeting N-linked Glycosylation for the Therapy of Aggressive Lymphomas.

Unlabelled: Diffuse large B-cell lymphoma (DLBCL) can be subdivided into the activated B-cell (ABC) and germinal center B cell-like (GCB) subtypes. Self-antigen engagement of B-cell receptors (BCR) in ABC tumors induces their clustering, thereby initiating chronic active signaling and activation of NF-κB and PI3 kinase. Constitutive BCR signaling is essential in some GCB tumors but primarily activates PI3 kinase.

Teacher Effects on Student Achievement and Height: A Cautionary Tale.

We apply "value-added" models to estimate the effects of teachers on an outcome they cannot plausibly affect: student height. When fitting commonly estimated models to New York City data, we find that the standard deviation of teacher effects on height is nearly as large as that for math and reading, raising potential concerns about value-added estimates of teacher effectiveness. We consider two explanations: non-random sorting of students to teachers and idiosyncratic classroom-level variation.

Adult Drosophila Lack Hematopoiesis but Rely on a Blood Cell Reservoir at the Respiratory Epithelia to Relay Infection Signals to Surrounding Tissues.

The use of adult Drosophila melanogaster as a model for hematopoiesis or organismal immunity has been debated. Addressing this question, we identify an extensive reservoir of blood cells (hemocytes) at the respiratory epithelia (tracheal air sacs) of the thorax and head. Lineage tracing and functional analyses demonstrate that the majority of adult hemocytes are phagocytic macrophages (plasmatocytes) from the embryonic lineage that parallels vertebrate tissue macrophages.

Efficient derivation of microglia-like cells from human pluripotent stem cells.

Microglia, the only lifelong resident immune cells of the central nervous system (CNS), are highly specialized macrophages that have been recognized to have a crucial role in neurodegenerative diseases such as Alzheimer's, Parkinson's and adrenoleukodystrophy (ALD). However, in contrast to other cell types of the human CNS, bona fide microglia have not yet been derived from cultured human pluripotent stem cells. Here we establish a robust and efficient protocol for the rapid production of microglia-like cells from human (h) embryonic stem (ES) and induced pluripotent stem (iPS) cells that uses defined serum-free culture conditions.

The Effect of Breakfast in the Classroom on Obesity and Academic Performance: Evidence from New York City.

Participation in the federally subsidized school breakfast program often falls well below its lunchtime counterpart. To increase take-up, many districts have implemented Breakfast in the Classroom (BIC), offering breakfast directly to students at the start of the school day. Beyond increasing participation, advocates claim BIC improves academic performance, attendance, and engagement.

Neighborhoods, Schools and Obesity: The Potential for Place-Based Approaches to Reduce Childhood Obesity.

A common policy approach to reducing childhood obesity aims to shape the environment in which children spend most of their time: neighborhoods and schools. This paper uses richly detailed data on the body mass index (BMI) of all New York City public school students in grades K-8 to assess the potential for place-based approaches to reduce child obesity. We document variation in the prevalence of obesity across NYC public schools and census tracts, and then estimate the extent to which this variation can be explained by differences in individual-level predictors (such as race and household income).

Not just for poor kids: The impact of universal free school breakfast on meal participation and student outcomes.

This paper examines the impact of the implementation of a universal free school breakfast policy on meals program participation, attendance, and academic achievement. In 2003, New York City made school breakfast free for all students regardless of income, while increasing the price of lunch for those ineligible for meal subsidies. Using a difference-indifference estimation strategy, we derive plausibly causal estimates of the policy's impact by exploiting within and between group variation in school meal pricing before and after the policy change.

The relative geographic immobility of new registered nurses calls for new strategies to augment that workforce.

Little is known about registered nurses' geographic mobility after they earn their first professional degree and become licensed to practice. Through a cross-sectional mailed survey of newly licensed registered nurses in fifteen states, we found that 52.5 percent work within forty miles of where they attended high school.

Commuting to work: RN travel time to employment in rural and urban areas.

Purpose: To investigate the variation in average daily travel time to work among registered nurses (RNs) living in urban, suburban, and rural areas. We examine how travel time varies across RN characteristics, job setting, and availability of local employment opportunities.

Method: Descriptive statistics and linear regression using a 5% sample from the 2000 Census and a longitudinal survey of newly licensed RNs (NLRN).