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We've all seen the oft-cited Gallup poll that reports that an alarming majority of the workforce is disengaged and unmotivated. In Alive at Work, social psychologist Dan Cable argues that the reason for all the unhappiness is biological: organizations, in an effort to routinize work and establish clear-cut performance metrics, are suppressing what neuroscientists call our Seeking Systems, the part of our brain that craves exploration and learning. The good news is that organizations can activate our Seeking Systems, and, as Cable explains, it doesn't take extensive overhauls to their cultures to do so. With small changes, managers and supervisors can make meaningful impacts on our lives and restore our zest for work. For instance, the book reveals: how new hires exhibited their best traits and were less likely to quit in the future after sharing stories about themselves during on-boarding seminars, how Italian factory workers reduced their anxiety about a new process by playing with Legos, how employees at Make-A-Wish reduced burnout by crafting their own job titles. Filled with real-life examples from the author's own research and consulting, Alive at Work equips managers--and anyone looking to find more joy in their nine-to-five existence--with the guidance to maximize the curiosity and passion that lives within themselves and others.-- Provided by publisher

A limitation of spatial transcriptomics technologies is that individual measurements may contain contributions from multiple cells, hindering the discovery of cell-type-specific spatial patterns of localization and expression. Here, we develop robust cell type decomposition (RCTD), a computational method that leverages cell type profiles learned from single-cell RNA-seq to decompose cell type mixtures while correcting for differences across sequencing technologies. We demonstrate the ability of RCTD to detect mixtures and identify cell types on simulated datasets. Furthermore, RCTD accurately reproduces known cell type and subtype localization patterns in Slide-seq and Visium datasets of the mouse brain. Finally, we show how RCTD’s recovery of cell type localization enables the discovery of genes within a cell type whose expression depends on spatial environment. Spatial mapping of cell types with RCTD enables the spatial components of cellular identity to be defined, uncovering new principles of cellular organization in biological tissue. RCTD is publicly available as an open-source R package at https://github.com/dmcable/RCTD . Cell type mapping in spatial transcriptomics is enabled by accounting for compositional mixtures and differences in sequencing technologies.

A central problem in spatial transcriptomics is detecting differentially expressed (DE) genes within cell types across tissue context. Challenges to learning DE include changing cell type composition across space and measurement pixels detecting transcripts from multiple cell types. Here, we introduce a statistical method, cell type-specific inference of differential expression (C-SIDE), that identifies cell type-specific DE in spatial transcriptomics, accounting for localization of other cell types. We model gene expression as an additive mixture across cell types of log-linear cell type-specific expression functions. C-SIDE’s framework applies to many contexts: DE due to pathology, anatomical regions, cell-to-cell interactions and cellular microenvironment. Furthermore, C-SIDE enables statistical inference across multiple/replicates. Simulations and validation experiments on Slide-seq, MERFISH and Visium datasets demonstrate that C-SIDE accurately identifies DE with valid uncertainty quantification. Last, we apply C-SIDE to identify plaque-dependent immune activity in Alzheimer’s disease and cellular interactions between tumor and immune cells. We distribute C-SIDE within the R package https://github.com/dmcable/spacexr . C-SIDE facilitates accurate cell type-specific differential expression analysis for multiple spatially resolved transcriptomics technologies by cell type mixture modeling.

Epstein-Barr Virus (EBV) is associated with numerous cancers including B cell lymphomas. In vitro , EBV transforms primary B cells into immortalized Lymphoblastoid Cell Lines (LCLs) which serves as a model to study the role of viral proteins in EBV malignancies. EBV induced cellular transformation is driven by viral proteins including EBV-Nuclear Antigens (EBNAs). EBNA-LP is important for the transformation of naïve but not memory B cells. While EBNA-LP was thought to promote gene activation by EBNA2, EBNA-LP Knockout (LPKO) virus-infected cells express EBNA2-activated cellular genes efficiently. Therefore, a gap in knowledge exists as to what roles EBNA-LP plays in naïve B cell transformation. We developed a trans-complementation assay wherein transfection with wild-type EBNA-LP rescues the transformation of peripheral blood- and cord blood-derived naïve B cells by LPKO virus. Despite EBNA-LP phosphorylation sites being important in EBNA2 co-activation; neither phospho-mutant nor phospho-mimetic EBNA-LP was defective in rescuing naïve B cell outgrowth. However, we identified conserved leucine-rich motifs in EBNA-LP that were required for transformation of adult naïve and cord blood B cells. Because cellular PPAR-g coactivator (PGC) proteins use leucine-rich motifs to engage transcription factors including YY1, a key regulator of DNA looping and metabolism, we examined the role of EBNA-LP in engaging transcription factors. We found a significant overlap between EBNA-LP and YY1 in ChIP-Seq data. By Cut&Run, YY1 peaks unique to WT compared to LPKO LCLs occur at more highly expressed genes. Moreover, Cas9 knockout of YY1 in primary B cells prior to EBV infection indicated YY1 to be important for EBV-mediated transformation. We confirmed EBNA-LP and YY1 biochemical association in LCLs by endogenous co-immunoprecipitation and found that the EBNA-LP leucine-rich motifs were required for YY1 interaction in LCLs. We propose that EBNA-LP engages YY1 through conserved leucine-rich motifs to promote EBV transformation of naïve B cells.

Spatial transcriptomics technologies permit the study of the spatial distribution of RNA at near-single-cell resolution genome-wide. However, the feasibility of studying spatial allele-specific expression (ASE) from these data remains uncharacterized. Here, we introduce spASE, a computational framework for detecting and estimating spatial ASE. To tackle the challenges presented by cell type mixtures and a low signal to noise ratio, we implement a hierarchical model involving additive mixtures of spatial smoothing splines. We apply our method to allele-resolved Visium and Slide-seq from the mouse cerebellum and hippocampus and report new insight into the landscape of spatial and cell type-specific ASE therein.

Phosphorus is an essential component for life, and in-situ identification of phosphate minerals that formed in aqueous conditions directly contributes toward one of the main goals of the Mars 2020 Perseverance rover: to seek signs of ancient habitable environments. In Jezero crater, proximity science analyses within a conglomerate outcrop, “ Onahu ” demonstrate the presence of rare Fe 3+ -bearing phosphate minerals (likely metavivianite, ferrolaueite, (ferro)beraunite, and/or santabarbaraite) embedded in a carbonate-rich matrix. While Fe-phosphates have been inferred previously on Mars, this work presents the most definitive in-situ identification of martian Fe-phosphate minerals to date, using textural, chemical, spectral, and diffraction analyses of discrete green-blue grains. The Fe-phosphate minerals’ textural context along with comparisons to Earth analogs suggest they likely formed after oxidation of Fe 2+ -phosphate vivianite, the most common Fe-phosphate in sedimentary environments on Earth, often associated with microbial activity and organics. While there is no obvious evidence of biological inputs in Onahu , if the Fe-phosphates’ formation environment was similar to vivianite-rich sedimentary environments on Earth, these minerals likely originally precipitated in conditions favorable to potential martian life — in a low temperature, reducing aqueous medium with high concentrations of bio-limiting elements, and Fe-redox gradients that could provide an energy source. If the sample collected from Onahu ( Otis_Peak ) is returned to Earth, analysis of the Fe-phosphates may provide new insights into ancient habitable environments on Mars. The Perseverance rover has made the most definitive identification of Fe-phosphate minerals on Mars to date. High-resolution chemical and textural PIXL analyses suggest they originally formed after vivianite in a potentially habitable environment.

Climate change predictions for the desert southwestern U.S. are for shifts in precipitation patterns. The impacts of climate change may be significant, because desert soil processes are strongly controlled by precipitation inputs (“pulses”) via their effect on soil water availability. This study examined the response of soil respiration--an important biological process that affects soil carbon (C) storage--to variation in pulses representative of climate change scenarios for the Sonoran Desert. Because deserts are mosaics of different plant cover types and soil textures--which create patchiness in soil respiration--we examined how these landscape characteristics interact to affect the response of soil respiration to pulses. Pulses were applied to experimental plots of bare and vegetated soil on contrasting soil textures typical of Sonoran Desert grasslands. The data were analyzed within a Bayesian framework to: (1) determine pulse size and antecedent moisture (soil moisture prior to the pulse) effects on soil respiration, (2) quantify soil texture (coarse vs. fine) and cover type (bare vs. vegetated) effects on the response of soil respiration and its components (plant vs. microbial) to pulses, and (3) explore the relationship between long-term variation in pulse regimes and seasonal soil respiration. Regarding objective (1), larger pulses resulted in higher respiration rates, particularly from vegetated fine-textured soil, and dry antecedent conditions amplified respiration responses to pulses (wet antecedent conditions dampened the pulse response). Regarding (2), autotrophic (plant) activity was a significant source (~60%) of respiration and was more sensitive to pulses on coarse- versus fine-textured soils. The sensitivity of heterotrophic (microbial) respiration to pulses was highly dependent on antecedent soil water. Regarding (3), seasonal soil respiration was predicted to increase with both growing season precipitation and mean pulse size (but only for pulses between 7 and 25 mm). Thus, the heterogeneity of the desert landscape and the timing or the number of medium-sized pulses is expected to significantly impact desert soil C loss with climate change.

Physiological activity and structural dynamics in arid and semi-arid ecosystems are driven by discrete inputs or \"pulses\" of growing season precipitation. Here we describe the short-term dynamics of ecosystem physiology in experimental stands of native (Heteropogon contortus) and invasive (Eragrostis lehmanniana) grasses to an irrigation pulse across two geomorphic surfaces with distinctly different soils: a Pleistocene-aged surface with high clay content in a strongly horizonated soil, and a Holocene-aged surface with low clay content in homogenously structured soils. We evaluated whole-ecosystem and leaf-level CO₂ and H₂O exchange, soil CO₂ efflux, along with plant and soil water status to understand potential constraints on whole-ecosystem carbon exchange during the initiation of the summer monsoon season. Prior to the irrigation pulse, both invasive and native grasses had less negative pre-dawn water potentials$(\\Psi_{{\\rm{pd}}})$greater leaf photosynthetic rates$(A_{{\\rm{net}}} )$and stomatal conductance$(g_{\\rm{s}} )$and greater rates of net ecosystem carbon exchange (NEE) on the Pleistocene surface than on the Holocene. Twenty-four hours following the experimental application of a 39 mm irrigation pulse, soil CO₂ efflux increased leading to all plots losing CO₂ to the atmosphere over the course of a day. Invasive species stands had greater evapotranspiration rates (ET) immediately following the precipitation pulse than did native stands, while maximum instantaneous NEE increased for both species and surfaces at roughly the same rate. The differential ET patterns through time were correlated with an earlier decline in NEE in the invasive species as compared to the native species plots. Plots with invasive species accumulated between 5% and 33% of the carbon that plots with the native species accumulated over the 15-day pulse period. Taken together, these results indicate that system CO₂ efflux (both the physical displacement of soil CO₂ by water along with plant and microbial respiration) strongly controls whole-ecosystem carbon exchange during precipitation pulses. Since CO₂ and H₂O loss to the atmosphere was partially driven by species effects on soil microclimate, understanding the mechanistic relationships between the soil characteristics, plant ecophysiological responses, and canopy structural dynamics will be important for understanding the effects of shifting precipitation and vegetation patterns in semi-arid environments.

Epstein-Barr virus (EBV) is a ubiquitous human virus that promotes B-cell activation and maturation through expression of latency proteins and non-coding RNAs. In this study, we provide evidence that EBV mimics the molecular phenotype of germinal center (GC) B cells. EBV infection of primary human B cells promotes their rapid proliferation and GC dark zone (DZ)-like gene expression profile. Following this transient hyperproliferative period, the activation of NF-κB target genes, including Bcl2a1 (BFL-1), simulates the transition from the DZ to the T-cell supported light zone (LZ). We previously characterized the regulatory landscape of EBV + B cells at the Bcl2a1 locus defining a key role for the viral EBV nuclear antigen (EBNA) 3A protein in promoting three-dimensional chromatin architecture correlated with BFL-1 expression. Here, we define the global chromatin accessibility of tonsillar B cells and find that naïve and memory B cells have highly similar accessibility profiles that differ substantially from those of DZ and LZ B cells. Notably, multiple regions within the Bcl2a1 locus are significantly more accessible in DZ and LZ versus naïve and memory subsets. However, we found that BFL-1 upregulation from DZ to LZ correlates with a significant increase in three-dimensional (3-D) chromatin association between accessible upstream enhancer regions and the BFL-1 transcriptional start site. These elements were critical for BFL-1 expression in lymphoblastoid cell lines (LCLs). Moreover, increased BFL-1 expression in LCLs protected against extrinsic apoptosis. Collectively, these results suggest a conserved mechanism underlying BFL-1 upregulation that promotes survival of both LZ and EBV + immortalized B cells. Epstein-Barr virus has evolved with its human host leading to an intimate relationship where infection of antibody-producing B cells mimics the process by which these cells normally recognize foreign antigens and become activated. Virtually everyone in the world is infected by adulthood and controls this virus pushing it into life-long latency. However, immune-suppressed individuals are at high risk for EBV+ cancers. Here, we isolated B cells from tonsils and compare the underlying molecular genetic differences between these cells and those infected with EBV. We find similar regulatory mechanism for expression of an important cellular protein that enables B cells to survive in lymphoid tissue. These findings link an underlying relationship at the molecular level between EBV-infected B cells in vitro with normally activated B cells in vivo . Our studies also characterize the role of a key viral control mechanism for B cell survival involved in long-term infection.