The rockefeller university

A goal of data visualization is to advance the understanding of multiparameter, large-scale datasets. In astrophysics, scientists map celestial objects to understand the hierarchical structure of the universe. In biology, genetic sequences and biological characteristics uncover evolutionary relationships and patterns (e.g., variation within species and ecological associations). Our highly interdisciplinary project entitled "A Cosmic View of Life on Earth" adapts an immersive astrophysics visualization platform called OpenSpace to contextualize diverse biological data. Dimensionality reduction techniques harmonize biological information to create spatial representations in which data are interactively explored on flat screens and planetarium domes. Visualizations are enriched with geographic metadata, 3-D scans of specimens, and species-specific sonifications (e.g., bird songs). The "Cosmic View" project eases the dissemination of stories related to biological domains (e.g., insects, birds, mammals, and human migrations) and facilitates scientific discovery.

Pregnancy brings about profound changes in the mammary gland to prepare for lactation, yet immunocyte changes that accompany this rapid remodeling are incompletely understood. We comprehensively analyzed mammary T cells, revealing a marked increase in CD4+ and CD8+ T effector cells, including an expansion of T cell receptor (TCR)alpha beta+CD8 alpha alpha+ cells, in pregnancy and lactation. T cells were localized in the mammary epithelium, resembling intraepithelial lymphocytes (IELs) typically found in mucosal tissues. Similarity to mucosal tissues was substantiated by demonstrating partial dependence on microbial cues, T cell migration from the intestine to the mammary gland in late pregnancy and shared TCR clonotypes between intestinal and mammary tissues, including intriguing public TCR families. Putative counterparts of mammary IELs were found in human breast and milk. Mammary IELs are thus poised to manage the transition from a nonmucosal tissue to a mucosal barrier during lactogenesis.

Genetic investigation in Mendelian skin disorders featuring generalized or localized skin scaling and redness, known as the ichthyoses, has revealed novel pathways relevant to epidermal integrity, barrier function, and desquamation. Here, we show that a recurrent de novo missense variant in EMP2 (epithelial membrane protein 2), which encodes a cell surface tetraspan protein in the growth- arrest specific 3 (GAS3)/peripheral myelin protein 22 (PMP22) family, is associated with a Mendelian skin disorder in the progressive symmetric erythrokeratoderma spectrum. The disorder features severely thickened, red, and scaly skin at sites of wound healing or repetitive movement including on the face, genitals, flexural areas, and the palms and soles. EMP2 has previously been shown to directly associate with focal adhesion kinase, which links cell junction forces to signaling pathways relevant to proliferation, migration, and wound healing. Using single- cell spatial transcriptomics in affected tissue, we found ectopic suprabasal activation of signaling pathways downstream of receptor tyrosine kinases including epidermal growth the key role of EMP2 in epidermal differentiation and proliferation.

Traditional chemical screens have focused on a single assay per screen, making them labor intensive and costly. Here, we combined a chemical screen with single-cell RNA sequencing (scRNA-seq) to perform Chemical Perturb-seq (ChemPerturb-seq), enabling a systematic analysis of the molecular changes of human beta cells upon individual small molecule treatments. Using this platform, we performed an in vivo barcoded screen and discovered a small molecule cocktail, including beta-lipotropin 61-91, insulin growth factor-1, and prostaglandin E2, with which preconditioning human beta cells and primary islets significantly enhanced function and survival when transplanted subcutaneously to female, but not to male, mice. We identified two additional molecules, serotonin and histamine, that promote islet function when transplanted subcutaneously to male mice using ChemPerturb-seq. Such small molecule cocktails could be applied to improve the current FDA-approved islet transplantation procedure. Finally, we developed an artificial intelligence (AI)-powered website, ChemPerturbDB, which provides user-friendly open access analysis of the extensive ChemPerturb-seq dataset.

Biomolecular condensates are key features of intracellular compartmentalization(1,2). As the most prominent nuclear condensate in eukaryotes, the nucleolus is a multiphase liquid-like structure in which ribosomal RNAs (rRNAs) are transcribed and processed, undergoing multiple maturation steps to form the small (SSU) and large (LSU) ribosomal subunits(3-5). However, how rRNA processing is coupled to the layered organization of the nucleolus is poorly understood owing to a lack of tools to precisely monitor and perturb nucleolar rRNA processing dynamics. Here we developed two complementary approaches to spatiotemporally map rRNA processing and engineer de novo nucleoli. Using sequencing in parallel with imaging, we found that rRNA processing steps are spatially segregated, with sequential maturation of rRNA required for its outward movement through nucleolar phases. By generating synthetic nucleoli in cells using an engineered rDNA plasmid system, we show that defects in SSU processing can alter the ordering of nucleolar phases, resulting in inside-out nucleoli and preventing rRNA outflux, while LSU precursors are necessary to build the outermost layer of the nucleolus. These findings demonstrate how rRNA is both a scaffold and substrate for the nucleolus, with rRNA acting as a programmable blueprint for the multiphase architecture that facilitates assembly of an essential molecular machine.

Epidermal stem cells produce the skin's barrier that excludes pathogens and prevents dehydration. Hair follicle stem cells (HFSCs) are dedicated to bursts of hair regeneration, but upon injury, they can also reconstruct, and thereafter maintain, the overlying epidermis. How HFSCs balance these fate choices to restore physiologic function to damaged tissue remains poorly understood. Here, we uncover serine as an unconventional, non-essential amino acid that impacts this process. When dietary serine dips, endogenous biosynthesis in HFSCs fails to meet demands (and vice versa), slowing hair cycle entry. Serine deprivation also alters wound repair, further delaying hair regeneration while accelerating re-epithelialization kinetics. Mechanistically, we show that HFSCs sense each fitness challenge by triggering the integrated stress response, which acts as a rheostat of epidermal-HF identity. As stress levels rise, skin barrier restoration kinetics accelerate while hair growth is delayed. Our findings offer potential for dietary and pharmacological intervention to accelerate wound healing.

Despite the f(0)(980) hadron having been discovered half a century ago, the question about its quark content has not been settled: it might be an ordinary quark-antiquark (q (q) over bar) meson, a tetraquark (q (q) over barq (q) over bar) exotic state, a kaon-antikaon (K (K) over bar) molecule, or a quark-antiquark-gluon (q (q) over barg) hybrid. This paper reports strong evidence that the f(0)(980) state is an ordinary q (q) over bar meson, inferred from the scaling of elliptic anisotropies (v(2)) with the number of constituent quarks (n(q)), as empirically established using conventional hadrons in relativistic heavy ion collisions. The f(0)(980) state is reconstructed via its dominant decay channel f(0)(980) -> pi(+)pi(-), in proton-lead collisions recorded by the CMS experiment at the LHC, and its v(2) is measured as a function of transverse momentum (p(T)). It is found that the n(q) = 2 (q (q) over bar state) hypothesis is favored over n(q) = 4 (q (q) over barq (q) over bar or K (K) over bar states) by 7.7, 6.3, or 3.1 standard deviations in the p(T) < 10, 8, or 6 GeV/c ranges, respectively, and over n(q) = 3 (q<(q)over bar>g hybrid state) by 3.5 standard deviations in the p(T) < 8GeV/c range. This result represents the first determination of the quark content of the f(0)(980) state, made possible by using a novel approach, and paves the way for similar studies of other exotic hadron candidates.

In the last two decades, metabolic and bariatric surgery (MBS) has become the mainstay of treatment for severe and complex obesity. The majority of patients undergoing MBS are women of childbearing age. Coupled with the dramatic increase in the utilization of MBS, caregivers are likely to encounter patients who have undergone MBS in routine practice. From this perspective, we highlight the different reproductive health challenges and issues encountered throughout the pre-operative, peri-operative, and postoperative phases.

Biomolecular condensates are key features of intracellular compartmentalization(1,2). As the most prominent nuclear condensate in eukaryotes, the nucleolus is a multiphase liquid-like structure in which ribosomal RNAs (rRNAs) are transcribed and processed, undergoing multiple maturation steps to form the small (SSU) and large (LSU) ribosomal subunits(3-5). However, how rRNA processing is coupled to the layered organization of the nucleolus is poorly understood owing to a lack of tools to precisely monitor and perturb nucleolar rRNA processing dynamics. Here we developed two complementary approaches to spatiotemporally map rRNA processing and engineer de novo nucleoli. Using sequencing in parallel with imaging, we found that rRNA processing steps are spatially segregated, with sequential maturation of rRNA required for its outward movement through nucleolar phases. By generating synthetic nucleoli in cells using an engineered rDNA plasmid system, we show that defects in SSU processing can alter the ordering of nucleolar phases, resulting in inside-out nucleoli and preventing rRNA outflux, while LSU precursors are necessary to build the outermost layer of the nucleolus. These findings demonstrate how rRNA is both a scaffold and substrate for the nucleolus, with rRNA acting as a programmable blueprint for the multiphase architecture that facilitates assembly of an essential molecular machine.