bluuebunny/crossref_metadata_2025_split huggingface dataset:
EHD2 overexpression promotes tumorigenesis and metastasis in triple-negative breast cancer by regulating store-operated calcium entry
Authors: Luan Haitao , Bielecki Timothy A. , Mohapatra Bhopal C. , Islam Namista , Mushtaq Insha , Bhat Aaqib M. , Mirza Sameer , Chakraborty Sukanya , Raza Mohsin , Storck Matthew D. , Toss Michael S. , Meza Jane L. , Thoreson Wallace B. , Coulter Donald W. , Rakha Emad A. , Band Vimla , Band Hamid 
Published: June 2022

AbstractWith nearly all cancer deaths a result of metastasis, elucidating novel pro-metastatic cellular adaptations could provide new therapeutic targets. Here, we show that overexpression of the EPS15-Homology Domain-containing 2 (EHD2) protein in a large subset of breast cancers (BCs), especially the triple-negative (TNBC) and HER2+ subtypes, correlates with shorter patient survival. The mRNAs for EHD2 and Caveolin-1/2, structural components of caveolae, show co-overexpression across breast tumors, predicting shorter survival in basal-like BC. EHD2 shRNA knockdown and CRISPR-Cas9 knockoutof EHD2, togetherwith mouse EHD2 rescue, in TNBC cell line models demonstrate a major positive role of EHD2 in promoting tumorigenesis and metastasis. Mechanistically, we link these roles of EHD2 to store-operated calcium entry (SOCE), with EHD2-dependent stabilization of plasma membrane caveolae ensuring high cell surface expression of the SOCE-linked calcium channel Orai1. The novel EHD2-SOCE oncogenic axis represents a potential therapeutic target in EHD2 and CAV1/2-overexpressing BC.
White matter and literacy: a dynamic system in flux
Authors: Roy Ethan , Richie-Halford Adam , Kruper John , Narayan Manjari , Bloom David , Nedelec Pierre , Sugrue Leo P. , Rauschecker Andreas , Brown Timothy T. , Jernigan Terry L. , McCandliss Bruce D. , Rokem Ariel , Yeatman Jason D. 
Published: June 2022

AbstractCross-sectional studies have linked differences in white matter tissue properties to reading skills. However, past studies have reported a range of, sometimes conflicting, results. Some studies suggest that white matter properties act as individual-level traits predictive of reading skill, whereas others suggest that reading skill and white matter develop as a function of an individual’s educational experience. In the present study, we tested two hypotheses: a) that diffusion properties of the white matter reflect stable brain characteristics that relate to reading skills over development or b) that white matter is a dynamic system, linked with learning over time. To answer these questions, we examined the relationship between white matter and reading in a five-year longitudinal dataset and a series of large-scale, single-observation, cross-sectional datasets (N=14,249 total participants). We find that gains in reading skill correspond to longitudinal changes in the white matter. However, in the single-observation datasets, we find no evidence for the hypothesis that individual differences in white matter predict reading skill. These findings highlight the link between dynamic processes in the white matter and learning.
Modeling the rarest of the rare: A comparison between joint species distribution models, ensembles of small models, and single-species models at extremely low sample sizes
Authors: Erickson Kelley D. , Smith Adam B. 
Published: June 2022

AbstractDetermining the distribution and environmental preferences of rare species threatened by global change has long been a focus of conservation. Typical minimum suggested number of occurrences ranges from ∼5 to 30, but many species are represented by even fewer occurrences. However, several newer methods may be able to accommodate such low samples sizes. These include Bayesian joint species distribution models (JSDMs) which allow rare species to statistically “borrow strength” from more common species with similar niches, and ensembles of small models (ESMs), which reduce the number of parameters by averaging smaller models. Here we explore how niche breadth and niche position relative to other species influence model performance at low sample sizes (N=2, 4, 8, 16, 32, 64) using virtual species within a community of real species. ESMs were better at discrimination tasks for most species, and yielded better-than-random accuracy even for N=2. In contrast, “traditional” single species or JSDMs were better able to estimate the underlying response curves of variables that influenced the niche, but at low sample sizes also were more likely to incorrectly identify unimportant factors as influential. Species with niches that were narrow and peripheral to the available environmental space yielded models with better discrimination capacity than species with broad niches or niches that were similar to those of other species, regardless of whether the modeling algorithm allowed for borrowing of strength. Our study suggests that some rare species may be able to be modeled reliably at very low sample sizes, although the best algorithm depends on number of occurrences and whether the niche or distribution is the focus.
Wildebeest Herds on Rolling Hills: Flocking on Arbitrary Curved Surfaces
Authors: Hueschen Christina L. , Dunn Alexander R. , Phillips Rob 
Published: June 2022

AbstractThe collective behavior of active agents, whether herds of wildebeest or microscopic actin filaments propelled by molecular motors, is an exciting frontier in biological and soft matter physics. Almost three decades ago, Toner and Tu developed a hydrodynamic theory of the collective action of flocks, or herds, that helped launch the modern field of active matter. One challenge faced when applying continuum active matter theories to living phenomena is the complex geometric structure of biological environments. Both macroscopic and microscopic herds move on asymmetric curved surfaces, like undulating grass plains or the surface layers of cells or embryos, which can render problems analytically intractable. In this work, we present a formulation of the Toner-Tu flocking theory that uses the finite element method to solve the governing equations on arbitrary curved surfaces. First, we test the developed formalism and its numerical implementation in channel flow with scattering obstacles and on cylindrical and spherical surfaces, comparing our results to analytical solutions. We then progress to surfaces with arbitrary curvature, moving beyond previously accessible problems to explore herding behavior on a variety of landscapes. Our approach allows the investigation of transients and dynamic solutions not revealed by analytic methods. It also enables versatile incorporation of new geometries and boundary conditions and efficient sweeps of parameter space. Looking forward, the work presented here lays the groundwork for a dialogue between Toner-Tu theory and data on collective motion in biologically-relevant geometries, from drone footage of migrating animal herds to movies of microscopic cytoskeletal flows within cells.
Intratumoral mregDC and CXCL13 T helper niches enable local differentiation of CD8 T cells following PD-1 blockade
Authors: Magen Assaf , Hamon Pauline , Fiaschi Nathalie , Troncoso Leanna , Humblin Etienne , D’souza Darwin , Dawson Travis , Park Matthew D. , Kim Joel , Hamel Steven , Buckup Mark , Chang Christie , Tabachnikova Alexandra , Schwartz Hara , Malissen Nausicaa , Lavin Yonit , Soares-Schanoski Alessandra , Giotti Bruno , Hegde Samarth , Mattiuz Raphaël , Hennequin Clotilde , Berichel Jessica Le , Zhao Zhen , Ward Stephen , Fiel Isabel , Price Colles , Fernandez Nicolas , He Jiang , Kou Baijun , Dobosz Michael , Li Lianjie , Adler Christina , Ni Min , Wei Yi , Wang Wei , Gupta Namita T. , Kundu Kunal , Cygan Kamil , Deering Raquel P. , Tsankov Alex , Kim-Schulze Seunghee , Gnjatic Sacha , Kenigsberg Ephraim , Schwartz Myron , Marron Thomas U. , Thurston Gavin , Kamphorst Alice O. , Merad Miriam 
Published: June 2022

ABSTRACTHere, we leveraged a large neoadjuvant PD-1 blockade trial in patients with hepatocellular carcinoma (HCC) to search for correlates of response to immune checkpoint blockade (ICB) within T cell-rich tumors. We show that ICB response correlated with the clonal expansion of intratumoral CXCL13+ CH25H+ IL-21+ PD-1+ CD4 T helper cells (CXCL13+ Th) and Granzyme K+ PD-1+ effector-like CD8 T cells, whereas terminally exhausted CD39hi TOXhi PD-1hi CD8 T cells dominated in non-responders. Strikingly, most T cell receptor (TCR) clones that expanded post-treatment were found in pre-treatment biopsies. Notably, PD-1+ TCF-1+ progenitor-like CD8 T cells were present in tumors of responders and non-responders and shared clones mainly with effector-like cells in responders or terminally differentiated cells in non-responders, suggesting that local CD8 T cell differentiation occurs upon ICB. We found that these progenitor CD8 T cells interact with CXCL13+ Th cells within cellular triads around dendritic cells enriched in maturation and regulatory molecules, or “mregDC”. Receptor-ligand analysis revealed unique interactions within these triads that may promote the differentiation of progenitor CD8 T cells into effector-like cells upon ICB. These results suggest that discrete intratumoral niches that include mregDC and CXCL13+ Th cells control the differentiation of tumor-specific progenitor CD8 T cell clones in patients treated with ICB.
A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury and matrix remodeling in patients with stone disease
Authors: Canela Victor Hugo , Bowen William S. , Ferreira Ricardo Melo , Lingeman James E. , Sabo Angela R. , Barwinska Daria , Winfree Seth , Lake Blue , Cheng Ying-Hua , LaFavers Kaice A. , Zhang Kun , Coe Fredric L. , Worcester Elaine , Jain Sanjay , Eadon Michael T. , Williams James C. , El-Achkar Tarek M. ,   the Kidney Precision Medicine Project
Published: June 2022

AbstractKidney stone disease causes significant morbidity and increases health care utilization. The pathogenesis of stone disease is not completely understood, due in part to the poor characterization of the cellular and molecular makeup of the kidney papilla and its alteration with disease. We deciphered the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease compared to healthy subjects using single nuclear RNA sequencing, spatial transcriptomics and high-resolution large-scale multiplexed 3D and Co-Detection by indexing (CODEX) imaging. In addition to identifying cell types important in papillary physiology, we defined subtypes of immune, stromal and principal cells enriched in the papilla, and characterized an undifferentiated epithelial cell cluster that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncovered a global injury signature involving multiple cell types within the papilla, characterized by immune activation, oxidative stress and extracellular matrix remodeling. The microenvironment of mineral deposition had features of an immune synapse with antigen presenting inflammatory macrophages interacting with T cells, and an immune repertoire ranging from inflammation to fibrosis. The expression of MMP7 and MMP9 was associated with stone disease and mineral deposition, respectively. MMP7 and MMP9 were significantly increased in the urine of patients with CaOx stone disease compared to non-stone formers, and their levels correlated with disease activity in stone formers. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla, and identify potential urinary biomarkers.
Membrane curvature governs the distribution of Piezo1 in live cells
Authors: Yang Shilong , Miao Xinwen , Arnold Steven , Li Boxuan , Ly Alan T. , Wang Huan , Wang Matthew , Guo Xiangfu , Pathak Medha M. , Zhao Wenting , Cox Charles D. , Shi Zheng 
Published: June 2022

AbstractPiezo1 is abona fidemechanosensitive ion channel ubiquitously expressed in mammalian cells. The distribution of Piezo1 within a cell is essential for various biological processes including cytokinesis, cell migration, and wound healing. However, the underlying principles that guide the subcellular distribution of Piezo1 remain largely unexplored. Here, we demonstrate that membrane curvature serves as a key regulator of the spatial distribution of Piezo1 in the plasma membrane of living cells. Piezo1 depletes from highly curved membrane protrusions such as filopodia and enriches to nanoscale membrane invaginations. Quantification of the curvaturedependent sorting of Piezo1 directly reveals thein situnano-geometry of the Piezo1-membrane complex. Piezo1 density on filopodia increases upon activation, independent of Ca2+, suggesting flattening of the channel upon opening. Consequently, the expression of Piezo1 inhibits filopodia formation, an effect that diminishes with channel activation.
Tumor-educated monocytes suppress T cells via adenosine and depletion of adenosine in the tumor microenvironment with adenosine deaminase enzyme promotes response to immunotherapy
Authors: Sarkar Omar S. , Donninger Howard , Rayyan Numan Al , Chew Lewis C. , Stamp Bryce , Zhang Xiang , Whitt Aaron , Li Chi , Hall Melissa , Mitchell Robert A. , Zippelius Alfred , Eaton John , Chesney Jason A. , Yaddanapudi Kavitha 
Published: June 2022

AbstractAlthough immune checkpoint inhibitor (ICI) therapy has provided robust results in many cancer types such as melanoma and lung cancer, a large percentage of patients remain unresponsive to this therapy. Emerging evidence strongly suggests that one of the contributing factors in ICI resistance is monocytic myeloid derived suppressor cells (M-MDSCs) that accumulate in late-stage cancer patients. These M-MDSCs are a subset of innate immune cells and possess potent immunosuppressive activity against T lymphocytes. Here we provide evidence of a mechanism by which CD73-expressing M-MDSCs in the tumor microenvironment (TME) exhibit superior T cell suppressor function via adenosine. We show that tumor-derived PGE2, a prostaglandin frequently found at high levels in the TME, directly induces CD73 expression in M-MDSCs by initiating a signaling pathway that is mediated by both Stat3 and CREB. The resulting CD73 overexpression induces elevated levels of adenosine, a nucleoside with strong T cell suppressive activity, culminating in the suppression of CD8+ T cell-mediated anti-tumor responses. We also show that depletion of adenosine in the TME by the repurposed drug PEGylated Adenosine Deaminase (PEG-ADA) increases CD8+ T cell anti-tumor activity and enhances response to ICI therapy in preclinical models of cancer. Our results suggest that use of PEG-ADA is a viable therapeutic option to overcome ICI therapeutic resistance in advanced cancer patients.
A self-blinking DNA probe for 3D superresolution imaging of native chromatin
Authors: Zheng Yang , Ye Sen , Li Shumin , Liu Cuifang , Luo Shihang , Xia Ruiqin , Chen Yanqin , Li Yunsheng , Zhu Zhenni , Huang Lingyi , Deng Shan , Yuen Karen Wing Yee , Chen Ping , Zhang Yongdeng , Ji Wei , Luo Ruibang , Li Guohong , Yang Dan 
Published: June 2022

ABSTRACTSingle-molecule localization microscopy is a powerful superresolution imaging technique to study biological questions by visualizing subcellular fine structures with nanometer-scale precision. However, its application in live-cell imaging studies has been impeded by the paucity of self-blinking organic fluorophores that enable high spatiotemporal resolution and labeling/localization density at a moderate laser intensity. Herein, we report a self-blinking Si-rhodamine dye6-HESiRwith a suitably increased “ON” fraction and a fluorogenic self-blinking dsDNA probe6-HoeHESiRas a powerful tool for 3D superresolution imaging of native chromatin in eukaryotes without the use of photoswitching buffer and high laser intensity. With the probe6-HoeHESiR, 3D superresolution imaging of in vitro reconstituted nucleosomal arrays and chromatin fibers yielded results consistent with EM analysis. Similar euchromatin and heterochromatin structures were visualized in fixed and live cells with high spatiotemporal resolution and labeling density, providing the first live-cell evidence for a hierarchical model of chromatin organization. 3D imaging results obtained in the presence of selective inhibitors of histone deacetylases also corroborate chromatin fiber decompaction upon hyperacetylation of histones.
Postsynaptic burst reactivation of hippocampal neurons enables associative plasticity of temporally discontiguous inputs
Authors: Fuchsberger Tanja , Clopath Claudia , Jarzebowski Przemyslaw , Brzosko Zuzanna , Wang Hongbing , Paulsen Ole 
Published: June 2022

AbstractA fundamental unresolved problem in neuroscience is how the brain associates in memory events that are separated in time. Here we propose that reactivation-induced synaptic plasticity can solve this problem. Previously, we reported that the reinforcement signal dopamine converts hippocampal spike timing-dependent depression into potentiation during continued synaptic activity (Brzosko et al., 2015). Here, we report that postsynaptic bursts in the presence of dopamine produces input-specific LTP in hippocampal synapses 10 minutes after they were primed with coincident pre- and postsynaptic activity. The priming activity sets an NMDAR-dependent silent eligibility trace which, through the cAMP-PKA cascade, is rapidly converted into protein synthesis-dependent synaptic potentiation, mediated by a signaling pathway distinct from that of conventional LTP. Incorporated into a computational model, this synaptic learning rule adds specificity to reinforcement learning by controlling memory allocation and enabling both ‘instructive’ and ‘supervised’ reinforcement learning. We predicted that this mechanism would make reactivated neurons activate more strongly and carry more spatial information than non-reactivated cells, which was confirmed in freely moving mice performing a reward-based navigation task.
Effects of Livestock Grazing Exclusion on Perennial Grasses and Woody Species on the San Pedro Riparian National Conservation Area, Arizona
Authors: Radke Marcia F. 
Published: June 2022

AbstractThe objective of this study was to determine the effects of livestock exclusion on native and non-native perennial grass richness and frequency, and woody species frequency on the San Pedro Riparian National Conservation Area. A significant increase in species richness of native perennial grass species was noted overall and in retired agricultural fields, supporting the hypothesis of increased species richness with grazing exclusion. There was a significant increase in the number of plots that contained an increase in bristlegrass (Setaria macrostachya Kunth and S. leucopila (Scribn. & Merr.) K. Schum.). No significant change in species richness of non-native invasive perennial grass species was observed. Lehmann lovegrass (Eragrostis lehmanniana Nees) had a significant increase in the number of plots that contained the species, supporting the hypothesis that Lehmann lovegrass expansion would occur in previously uninvaded areas even without current livestock grazing. Velvet mesquite (Prosopis velutina Wooton) exhibited a significant increase in canopy frequency, but velvet mesquite basal frequency showed no significant increase or decrease. Results indicate that past grazing was a primary factor leading to the current distribution and density of mesquite on the SPRNCA because the same basal (i.e. rooted stem) frequency existed prior to and after grazing exclusion. Management considerations include continued grazing exclusion, inventory and monitoring of pollinator plants, continued monitoring of pace frequency transects, use of prescribed fire in uplands, monitoring of soil erosion, and implementation of erosion controls.
PIEZO1 discriminates mechanical stimuli
Authors: Ozkan Alper D. , Wijerathne Tharaka D. , Gettas Tina , Lacroix Jérôme J. 
Published: June 2022

AbstractPIEZO1 channels open in response to numerous mechanical stimuli, such as physical membrane deformations, which modulate the curvature of flexible domains called blades. Yet, whether different stimuli cause similar blade motions and whether these rearrangements correlate with pore opening remain unclear. Here, we scan local conformational changes along the PIEZO1 blade using fluorescent probes. We identify two distant probes, one intracellular proximal and the other extracellular distal, which independently and robustly respond to flow stimuli. Flow-induced signals from both probes exquisitely correlate with PIEZO1-dependent calcium influx and specifically increase in presence of fast-inactivating pore mutations. In contrast, both probes remain fluorimetrically silent to hypotonic shocks and indentations, two stimuli that otherwise evoke normal electrochemical responses in both engineered channels. This study reveals that flow-induced blade motions are functionally coupled to the pore and that at least two distant blade regions discriminate flow from two other stimuli, suggesting that PIEZO1 mobilizes distinct mechanisms to sense a broad range of mechanical cues.TeaserFluorimetric evidence suggests that different mechanical stimuli impart distinct rearrangements in PIEZO1’s mechanosensory domains.
Rational selection and Characterisation of bile acid (BA) metabolising species of infant origin
Authors: Long Sarah L. , Joyce Susan A. 
Published: June 2022

ABSTRACTBile acids (BAs), biological detergents for nutrient digestion, are important local and systemic signalling molecules to interact with a variety of cell receptors central to influence host responses. While BAs are synthesized in the liver, the range and diversity of bile acids available to interact with these receptors is dictated by the gut microbiota. Bile salt hydrolase (BSH) activity is one such function, it is commonly represented and highly conserved across all major bacterial phyla in the gut. Studies relating to the importance of such modifications in early life are scarce. This study highlights BA metabolism diversity by functionally isolating BA metabolizing strains and by characterizing specific classes of BSH from the formula–fed transitioning gut. Isolates were identified to species levels,in silicoandin vitrocharacterisation of their BSH genetic content, enzyme activity and substrate specificity. One of these isolates was identified asLactobacillus acidophilus, a species frequently applied as a probiotic whereas three of these four isolates were identified asEnterococcus avium. This particular species is not well characterized in the literature and to our knowledge this is the first report of BSH activity and assessment for probiotic potential within this class of microbes. This study indicates that microbial BA altering activity appears functionally reduced, in the formula fed infant gut.