A whole-cell platform for discovering synthetic cell adhesion molecules in bacteria.

Developing programmable bacterial cell-cell adhesion is of significant interest due to its versatile applications. Current methods that rely on presenting cell adhesion molecules (CAMs) on bacterial surfaces are limited by the lack of a generalizable strategy to identify such molecules targeting bacterial membrane proteins in their natural states. Here, we introduce a whole-cell screening platform designed to discover CAMs targeting bacterial membrane proteins within a synthetic bacteria-displayed nanobody library.

The epithelial axis is an essential regulator of gut inflammation, energy metabolism, and the microbiome.

Chronic inflammation is epidemiologically linked to the pathogenesis of gastrointestinal diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, our understanding of the molecular mechanisms controlling gut inflammation remains insufficient, hindering the development of targeted therapies for IBD and CRC. In this study, we uncovered as a negative regulator of gut inflammation, operating through the modulation of epithelial cell metabolism.

Designing an Observing System to Study the Surface Biology and Geology (SBG) of the Earth in the 2020s.

Observations of planet Earth from space are a critical resource for science and society. Satellite measurements represent very large investments and United States (US) agencies organize their effort to maximize the return on that investment. The US National Research Council conducts a survey of Earth science and applications to prioritize observations for the coming decade.

Design and synthesis of fascaplysin derivatives as inhibitors of FtsZ with potent antibacterial activity and mechanistic study.

The increase in antibiotic resistance has made it particularly urgent to develop new antibiotics with novel antibacterial mechanisms. Inhibition of bacterial cell division by disrupting filamentous temperature-sensitive mutant Z (FtsZ) function is an effective and promising approach. A series of novel fascaplysin derivatives with tunable hydrophobicity were designed and synthesized here.

A Cre-deleter specific for embryo-derived brain macrophages reveals distinct features of microglia and border macrophages.

Genetic tools to target microglia specifically and efficiently from the early stages of embryonic development are lacking. We generated a constitutive Cre line controlled by the microglia signature gene Crybb1 that produced nearly complete recombination in embryonic brain macrophages (microglia and border-associated macrophages [BAMs]) by the perinatal period, with limited recombination in peripheral myeloid cells. Using this tool in combination with Flt3-Cre lineage tracer, single-cell RNA-sequencing analysis, and confocal imaging, we resolved embryonic-derived versus monocyte-derived BAMs in the mouse cortex.

Greening of human-dominated ecosystems in India.

Satellite data show the Earth has been greening and identify croplands in India as one of the most prominent greening hotspots. Though India's agriculture has been dependent on irrigation enhancement to reduce crop water stress and increase production, the spatiotemporal dynamics of how irrigation influenced the satellite observed greenness remains unclear. Here, we use satellite-derived leaf area data and survey-based agricultural statistics together with results from state-of-the-art Land Surface Models (LSM) to investigate the role of irrigation in the greening of India's croplands.

NASA Global Daily Downscaled Projections, CMIP6.

We describe the latest version of the NASA Earth Exchange Global Daily Downscaled Projections (NEX-GDDP-CMIP6). The archive contains downscaled historical and future projections for 1950-2100 based on output from Phase 6 of the Climate Model Intercomparison Project (CMIP6). The downscaled products were produced using a daily variant of the monthly bias correction/spatial disaggregation (BCSD) method and are at 1/4-degree horizontal resolution.

The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4 eosinophils unique to the small intestine.

C-type lectin domain family 4, member a4 (Clec4a4) is a C-type lectin inhibitory receptor specific for glycans thought to be exclusively expressed on murine CD8α− conventional dendritic cells. Using newly generated Clec4a4-mCherry knock-in mice, we identify a subset of Clec4a4-expressing eosinophils uniquely localized in the small intestine lamina propria. Clec4a4+ eosinophils evinced an immunomodulatory signature, whereas Clec4a4− eosinophils manifested a proinflammatory profile.

A Framework for Deep Learning Emulation of Numerical Models With a Case Study in Satellite Remote Sensing.

Numerical models based on physics represent the state of the art in Earth system modeling and comprise our best tools for generating insights and predictions. Despite rapid growth in computational power, the perceived need for higher model resolutions overwhelms the latest generation computers, reducing the ability of modelers to generate simulations for understanding parameter sensitivities and characterizing variability and uncertainty. Thus, surrogate models are often developed to capture the essential attributes of the full-blown numerical models.

Whole-genome profiling of DNA methylation and hydroxymethylation identifies distinct regulatory programs among innate lymphocytes.

Innate lymphocytes encompass a diverse array of phenotypic identities with specialized functions. DNA methylation and hydroxymethylation are essential for epigenetic fidelity and fate commitment. The landscapes of these modifications are unknown in innate lymphocytes.

microRNA-142 guards against autoimmunity by controlling Treg cell homeostasis and function.

Regulatory T (Treg) cells are critical in preventing aberrant immune responses. Posttranscriptional control of gene expression by microRNA (miRNA) has recently emerged as an essential genetic element for Treg cell function. Here, we report that mice with Treg cell-specific ablation of miR-142 (hereafter Foxp3CremiR-142fl/fl mice) developed a fatal systemic autoimmune disorder due to a breakdown in peripheral T-cell tolerance.

Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders.

The meninges contain adaptive immune cells that provide immunosurveillance of the central nervous system (CNS). These cells are thought to derive from the systemic circulation. Through single-cell analyses, confocal imaging, bone marrow chimeras, and parabiosis experiments, we show that meningeal B cells derive locally from the calvaria, which harbors a bone marrow niche for hematopoiesis.

New generation geostationary satellite observations support seasonality in greenness of the Amazon evergreen forests.

Assessing the seasonal patterns of the Amazon rainforests has been difficult because of the paucity of ground observations and persistent cloud cover over these forests obscuring optical remote sensing observations. Here, we use data from a new generation of geostationary satellites that carry the Advanced Baseline Imager (ABI) to study the Amazon canopy. ABI is similar to the widely used polar orbiting sensor, the Moderate Resolution Imaging Spectroradiometer (MODIS), but provides observations every 10-15 min.

MicroRNA-142 Is Critical for the Homeostasis and Function of Type 1 Innate Lymphoid Cells.

Natural killer (NK) cells are cytotoxic type 1 innate lymphoid cells (ILCs) that defend against viruses and mediate anti-tumor responses, yet mechanisms controlling their development and function remain incompletely understood. We hypothesized that the abundantly expressed microRNA-142 (miR-142) is a critical regulator of type 1 ILC biology. Interleukin-15 (IL-15) signaling induced miR-142 expression, whereas global and ILC-specific miR-142-deficient mice exhibited a cell-intrinsic loss of NK cells.

- regulatory axis controls autoimmunity and myelopoiesis, but is dispensable for hematopoietic stem cell homeostasis and tumor suppression.

() has been previously implicated as an essential molecular brake, preventing immune overreaction and malignant transformation by attenuating NF-κB signaling, putatively via repression of the and genes. The exact contribution of -mediated silencing of these genes to the control of immune activation is currently unknown. Therefore, we defined the role of the - signaling axis in the regulation of immune homeostasis using a genetic epistasis analysis in mice.

Global patterns and controls of soil organic carbon dynamics as simulated by multiple terrestrial biosphere models: Current status and future directions.

Soil is the largest organic carbon (C) pool of terrestrial ecosystems, and C loss from soil accounts for a large proportion of land-atmosphere C exchange. Therefore, a small change in soil organic C (SOC) can affect atmospheric carbon dioxide (CO) concentration and climate change. In the past decades, a wide variety of studies have been conducted to quantify global SOC stocks and soil C exchange with the atmosphere through site measurements, inventories, and empirical/process-based modeling.

Altered lymphopoiesis and immunodeficiency in miR-142 null mice.

MicroRNAs (miRNAs) are a class of powerful posttranscriptional regulators implicated in the control of diverse biological processes, including regulation of hematopoiesis and the immune response. To define the biological functions of miR-142, which is preferentially and abundantly expressed in immune cells, we created a mouse line with a targeted deletion of this gene. Our analysis of miR-142(-/-) mice revealed a critical role for this miRNA in the development and homeostasis of lymphocytes.

Variations in atmospheric CO2 growth rates coupled with tropical temperature.

Previous studies have highlighted the occurrence and intensity of El Niño-Southern Oscillation as important drivers of the interannual variability of the atmospheric CO2 growth rate, but the underlying biogeophysical mechanisms governing such connections remain unclear. Here we show a strong and persistent coupling (r(2) ≈ 0.50) between interannual variations of the CO2 growth rate and tropical land-surface air temperature during 1959 to 2011, with a 1 °C tropical temperature anomaly leading to a 3.

A large proportion of North American net ecosystem production is offset by emissions from harvested products, river/stream evasion, and biomass burning.

Diagnostic carbon cycle models produce estimates of net ecosystem production (NEP, the balance of net primary production and heterotrophic respiration) by integrating information from (i) satellite-based observations of land surface vegetation characteristics; (ii) distributed meteorological data; and (iii) eddy covariance flux tower observations of net ecosystem exchange (NEE) (used in model parameterization). However, a full bottom-up accounting of NEE (the vertical carbon flux) that is suitable for integration with atmosphere-based inversion modeling also includes emissions from decomposition/respiration of harvested forest and agricultural products, CO2 evasion from streams and rivers, and biomass burning. Here, we produce a daily time step NEE for North America for the year 2004 that includes NEP as well as the additional emissions.

R26R-GR: a Cre-activable dual fluorescent protein reporter mouse.

Green fluorescent protein (GFP) and its derivatives are the most widely used molecular reporters for live cell imagining. The development of organelle-specific fusion fluorescent proteins improves the labeling resolution to a higher level. Here we generate a R26 dual fluorescent protein reporter mouse, activated by Cre-mediated DNA recombination, labeling target cells with a chromatin-specific enhanced green fluorescence protein (EGFP) and a plasma membrane-anchored monomeric cherry fluorescent protein (mCherry).