bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microglial remodeling of actin network by Tau oligomers, via G protein‐coupled purinergic receptor, P2Y12R‐driven chemotaxis
Authors: Das Rashmi , Chinnathambi Subashchandrabose 
Published: February 2021

AbstractAlzheimer's disease (AD) is associated with age‐related neurodegeneration, synaptic deformation and chronic inflammation mediated by microglia and infiltrated macrophages in the brain. Tau oligomers can be released from damaged neurons via various mechanisms such as exosomes, neurotransmitter, membrane leakage etc. Microglia sense the extracellular Tau through several cell‐surface receptors and mediate chemotaxis and phagocytosis. The purinergic receptor P2Y12R recently gained interest in neurodegeneration for neuro‐glial communication and microglial chemotaxis towards the site of plaque deposition. To understand the effect of extracellular Tau oligomers in microglial migration, the P2Y12R‐mediated actin remodeling, reorientation of tubulin network and rate of migration were studied in the presence of ATP. The extracellular Tau species directly interacted with P2Y12R and also induced this purinoceptor expression in microglia. Microglial P2Y12R colocalized with remodeled membrane‐associated actin network as a component of migration in response to Tau oligomers. As an inducer of P2Y12R, ATP facilitated the localization of P2Y12R in lamellipodia and filopodia during accelerated microglial migration. The direct interaction of extracellular Tau oligomers with microglial P2Y12R would facilitate the signal transduction in both way, directional chemotaxis and receptor‐mediated phagocytosis. These unprecedented findings emphasize that microglia can modulate the membrane‐associated actin structure and incorporate P2Y12R to perceive the axis and rate of chemotaxis in Tauopathy.
SARS‐CoV‐2 seroprevalence among blood donors after the first COVID‐19 wave in Canada
Authors: Saeed Sahar , Drews Steven J. , Pambrun Chantale , Yi Qi‐Long , Osmond Lori , O'Brien Sheila F. 
Published: February 2021

AbstractBackgroundCase detection underestimates the burden of the COVID‐19 pandemic. Following the first COVID‐19 wave, we estimated the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) among blood donors across Canada.Study Design and MethodsThis serial cross‐sectional study was conducted between May 9 and July 21, 2020 from blood donors donating at all Canadian Blood Services locations. We used the Abbott Architect assay to detect SARS‐CoV‐2 IgG antibodies from retention plasma. Seroprevalence was standardized to population‐level demographics and assay characteristics were adjusted using the Rogan‐Gladen equation. Results were stratified by region, age, ethnicity, ABO groups, and quantiles of material and social deprivation indices. Temporal trends were evaluated at 2‐week intervals. Univariate and multivariate logistic regression compared SARS‐CoV‐2 reactive to non‐reactive donors by sociodemographic variables.ResultsOverall 552/74642 donors, had detectable antibodies, adjusted seroprevalence was 7.0/1000 donors (95% CI; 6.3, 7.6). Prevalence was differential by geography, Ontario had the highest rate, 8.8/1000 donors (7.8, 9.8), compared to the Atlantic region 4.5/1000 donors (2.6, 6.4); adjusted odds ratio (aOR) 2.2 (1.5, 3.3). Donors that self‐identified as an ethnic minority were more likely than white donors to be sero‐reactive aOR 1.5 (1.2, 1.9). No temporal trends were observed.DiscussionWorldwide, blood services have leveraged their operational capacity to inform public health. While >99% of Canadians did not show humoral evidence of past infection, we found regional variability and disparities by ethnicity. Seroprevalence studies will continue to play a pivotal role in evaluating public health policies by identifying trends and monitor disparities.
Effect of Dispersant Concentration With Friction Modifiers and Anti-Wear Additives on the Tribofilm Composition and Boundary Friction
Authors: Umer J. , Morris N. J. , Rahmani R. , Rahnejat H. , Howell-Smith S. , Balakrishnan S. 
Published: February 2021

Abstract
To extend drain intervals and improve efficiency, new engine oils with increased dispersant concentration and reduced viscosity are required. Low viscosity engine oils can increase the prevalence of boundary friction at low temperature and increase its severity at higher temperatures. As a result, combinations of organic and inorganic friction modifiers (FM) will be used to reduce boundary friction across a range of temperatures, also preventing damage to vehicle catalysts. This paper presents an experimental case study of such a new generation of fully formulated engine lubricants with varying concentrations of polyisobutylene succinimide dispersant, organic, and inorganic FM. Representative conditions pertaining to those encountered at the top dead center reversal of the piston compression ring-cylinder liner contact are created, and the generated friction measured through use of a sliding-strip tribometry. Subsequently, X-ray photoelectron spectroscopy (XPS) is used to determine the composition of the formed surface tribofilms in order to explain the observed frictional characteristics. The key interactions and frictional behavior of the dispersant and friction modifiers are highlighted across a range of operating temperatures.
Load-Bearing Capacity Investigation of Friction Pairs in Hydro-Viscous Drive Based on Fractal Contact Theory
Authors: Cui Hong-Wei , Jiang Yu-Yu , Wang Qi-Liang 
Published: February 2021

Abstract
Hydro-viscous drive has gained extensive application in fans, pumps, belt conveyors, and scraper conveyors for step-less speed regulating, soft starting, and overload protection. In the mixed friction stage, the state of contact and load-bearing capacity are always changing with the pressure of control oil. In order to predict the load-bearing capacity of friction pairs, a description of the frictional and hydrodynamic lubrication states was first made. Oil film’s pressure distribution and load-bearing capacity were analyzed with the average flow model. The fractal contact model of the asperity surface was proposed for simulating mutual contact state and contact load between the asperities. The influences of fractal parameters on the contact performance of friction pairs were conducted. Eventually, test rig of load-bearing capacity was established. As indicated by the experiment, asperity contact area and load-bearing capacity of the asperity contact increase slowly at first and then rapidly with reduced film thickness ratio. Correspondingly, oil film load-bearing capacity progressively reduces. Due to the reduction of film thickness ratio, friction pairs’ load-bearing capacity increases gradually. The load-bearing capacity of friction pairs is affected by the fractal dimension and scale factor. Results of the experiment well conform to the theoretical values, which illustrates that friction pairs’ load-bearing capacity can be accurately predicted and computed using the average flow model and M-B fractal contact model. The calculation offers a theoretical reference to the survey about friction and torque properties of the hydro-viscous drive.
Draft Genome Sequence of Vogesella oryzae L3B39
T
, Isolated from the Rhizosphere of Saline-Tolerant Pokkali Rice
Authors: Kangale Luis Johnson , Levasseur Anthony , Anani Hussein , Raoult Didier , Ghigo Eric , Fournier Pierre-Edouard 
Published: February 2021

Here, we report the draft genome sequence of
Vogesella oryzae
L3B39
T
(CSUR Q2602
T
= DSM 28780), which is a
Vogesella
species isolated from the rhizosphere of saline-tolerant pokkali rice. The genome sequence was assembled into 58 contigs for a total size of 3,415,129 bp, with a G+C content of 62.3%.
Chapter 3.2b Bransfield Strait and James Ross Island: petrology
Authors: Haase Karsten M. , Beier Christoph 
Published: February 2021

Abstract
Young volcanic centres of the Bransfield Strait and James Ross Island occur along back-arc extensional structures parallel to the South Shetland island arc. Back-arc extension was caused by slab rollback at the South Shetland Trench during the past 4 myr. The variability of lava compositions along the Bransfield Strait results from varying degrees of mantle depletion and input of a slab component. The mantle underneath the Bransfield Strait is heterogeneous on a scale of approximately tens of kilometres with portions in the mantle wedge not affected by slab fluids. Lavas from James Ross Island east of the Antarctic Peninsula differ in composition from those of the Bransfield Strait in that they are alkaline without evidence for a component from a subducted slab. Alkaline lavas from the volcanic centres east of the Antarctic Peninsula imply variably low degrees of partial melting in the presence of residual garnet, suggesting variable thinning of the lithosphere by extension. Magmas in the Bransfield Strait form by relatively high degrees of melting in the shallow mantle, whereas the magmas some 150 km further east form by low degrees of melting deeper in the mantle, reflecting the diversity of mantle geodynamic processes related to subduction along the South Shetland Trench.
Progesterone-induced blocking factor improves blood pressure, inflammation, and pup weight in response to reduced uterine perfusion pressure (RUPP)
Authors: Cottrell Jesse N. , Witcher Alexis C. , Comley Kyleigh , Cunningham Jr. Mark W. , Ibrahim Tarek , Cornelius Denise C. , LaMarca Babbette , Amaral Lorena M. 
Published: February 2021

Preeclampsia (PE) is characterized by new-onset hypertension in association with elevated natural killer (NK) cells and inflammatory cytokines, which are likely culprits for decreased fetal weight during PE pregnancies. As progesterone increases during normal pregnancy, it stimulates progesterone-induced blocking factor (PIBF). PIBF has been shown to decrease inflammation and cytolytic NK cells, both of which are increased during PE. We hypothesized that PIBF reduces inflammation as a mechanism to improve hypertension in the preclinical reduced uterine perfusion pressure (RUPP) rat model of PE. PIBF (2.0 µg/mL) was administered intraperitoneally on gestational day 15 to either RUPP or normal pregnant (NP) rats. On day 18, carotid catheters were inserted. Mean arterial blood pressure (MAP) and samples were collected on day 19. MAP in NP rats ( n = 11) was 100 ± 2 mmHg and 105 ± 3 mmHg in NP + PIBF rats ( n = 8) and 122 ± 1 mmHg in RUPP rats ( n = 10), which improved to 110 ± 2 mmHg in RUPP + PIBF rats ( n = 11), P < 0.05. Pup weight was 2.4 ± 0.1 g in NP, 2.5 ± 0.1 g in NP + PIBF, 1.9 ± 0.1 g in RUPP, and improved to 2.1 ± 0.1 g in RUPP + PIBF rats. Circulating and placental cytolytic NK cells, IL-17, and IL-6 were significantly reduced while IL-4 and T helper (TH) 2 cells were significantly increased in RUPP rats after PIBF administration. Importantly, vasoactive pathways preproendothelin-1, nitric oxide, and soluble fms-Like tyrosine Kinase-1 (sFlt-1) were normalized in RUPP + PIBF rats compared with RUPP rats, P < 0.05. Our findings suggest that PIBF normalized IL-4/TH2 cells, which was associated with improved inflammation, fetal growth restriction, and blood pressure in the RUPP rat model of PE.
Identification of biomarkers for tumor endothelial cell proliferation through gene expression profiling
Authors: Hardwick James S. , Yang Yi , Zhang Chunsheng , Shi Bin , McFall Rosemary , Koury Elizabeth J. , Hill Susan L. , Dai Hongyue , Wasserman Robert , Phillips Robert L. , Weinstein Edward J. , Kohl Nancy E. , Severino Michael E. , Lamb John R. , Sepp-Lorenzino Laura 
Published: February 2021

AbstractExtensive efforts are under way to identify antiangiogenic therapies for the treatment of human cancers. Many proposed therapeutics target vascular endothelial growth factor (VEGF) or the kinase insert domain receptor (KDR/VEGF receptor-2/FLK-1), the mitogenic VEGF receptor tyrosine kinase expressed by endothelial cells. Inhibition of KDR catalytic activity blocks tumor neoangiogenesis, reduces vascular permeability, and, in animal models, inhibits tumor growth and metastasis. Using a gene expression profiling strategy in rat tumor models, we identified a set of six genes that are selectively overexpressed in tumor endothelial cells relative to tumor cells and whose pattern of expression correlates with the rate of tumor endothelial cell proliferation. In addition to being potential targets for antiangiogenesis tumor therapy, the expression patterns of these genes or their protein products may aid the development of pharmacodynamic assays for small molecule inhibitors of the KDR kinase in human tumors.
Mystery Checkpoint Revealed: KIR3DL3 Finally Found a Ligand in HHLA2
Authors: Campbell Kerry S. 
Published: February 2021

Abstract

Inhibitory killer cell immunoglobulin–like receptors (iKIR) tolerize natural killer cells and some T cells upon detecting classical HLA class I molecules. In this issue, Bhatt and colleagues identify the B7 family member HHLA2 as an unanticipated ligand for a peculiar iKIR family member, KIR3DL3. These data establish a new inhibitory checkpoint pathway that may protect HHLA2+ tumor cells from immune attack.
See article by Bhatt et al., p. 156
Abstract IA04: Targeting macrophages to promote anti-tumor immunity
Authors: Varner Judith A. 
Published: February 2021

Abstract
Macrophages accumulate rapidly in tumors, where they promote immune suppression, tumor growth and resistance to therapy. Strategies to inhibit macrophage accumulation by blocking their recruitment from circulation have had limited therapeutic success. We found that the majority of macrophages in aggressive solid tumors accumulate by proliferation from c-Kit dependent tissue resident macrophages, rather than by trafficking from the circulation. Tissue resident macrophages express signatures of proliferation and profound immune suppression that correlate with unfavorable outcomes in cancer patients. By comparison, bone marrow derived macrophages express mixed signatures of inflammation and immune suppression that correlate with more favorable clinical outcomes. Genetic and pharmacological inhibition of proliferation mechanisms suppressed the expansion of these macrophages, thereby limiting their accumulation in tumors and inhibiting tumor progression in mouse models of cancer. These results identify macrophage proliferation is a new target for the development of therapeutic strategies to stimulate anti-cancer immunity.
Citation Format: Judith A. Varner. Targeting macrophages to promote anti-tumor immunity [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr IA04.
Abstract IA09: The IRE1 ER stress sensor activates natural killer cell immunity by regulating c-Myc
Authors: Glimcher Laurie H. 
Published: February 2021

Abstract
Natural killer (NK) cells are critical mediators of host immunity to pathogens. Here, we demonstrate that the endoplasmic retic- ulum stress sensor inositol-requiring enzyme 1 (IRE1α) and its substrate transcription factor X-box-binding protein 1 (XBP1) drive NK cell responses against viral infection and tumors in vivo. IRE1α-XBP1 were essential for expansion of activated mouse and human NK cells and are situated downstream of the mammalian target of rapamycin signaling pathway. Transcriptome and chromatin immunoprecipitation analysis revealed c-Myc as a new and direct downstream target of XBP1 for regulation of NK cell proliferation. Genetic ablation or pharmaceutical blockade of IRE1α downregulated c-Myc, and NK cells with c-Myc haplo- insufficency phenocopied IRE1α-XBP1 deficiency. c-Myc overexpression largely rescued the proliferation defect in IRE1α−/− NK cells. Like c-Myc, IRE1α-XBP1 also promotes oxidative phosphorylation in NK cells. Overall, our study identifies a IRE1α-XBP1- cMyc axis in NK cell immunity, providing insight into host protection against infection and cancer.
Citation Format: Laurie H. Glimcher. The IRE1 ER stress sensor activates natural killer cell immunity by regulating c-Myc [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr IA09.
Abstract IA10: Building improved personal cancer vaccines
Authors: Wu Catherine J. 
Published: February 2021

Abstract
Multiple lines of evidence have convincingly demonstrated tumor neoantigens as an important class of immunogenic tumor antigens, and have motivated the development of personalized cancer neoantigen targeting approaches. Neoantigens arise from amino acid changes encoded by somatic mutations in the tumor cell and have the potential to bind to and be presented by personal HLA molecules. Because the immune response has the capacity of addressing multiple tumor neoantigens simultaneously, immune-based therapy has a potential for directly address tumor heterogeneity. As a field, we have now successfully moved beyond the first wave proof-of-concept studies that have demonstrated the safety, feasibility and high immunogenicity of these personalized neoantigen-targeting vaccines. An imperative now is to address the challenges of discovering and optimizing the selection of antigens to target, the delivery approach, and extending this promising approach to a broader array of cancer settings.
Citation Format: Catherine J. Wu. Building improved personal cancer vaccines [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr IA10.
Abstract IA13: The future of CAR therapies
Authors: Shpall Elizabeth J. 
Published: February 2021

Abstract
Great progress has been made in the development of clinical CAR-T cell therapies. The autologous CAR-T cell approaches in the clinic today are extremely effective but have been associated with significant toxicities and are very expensive. The use of allogeneic, off-the-shelf CAR therapies using natural killer cells from several different sources will be reviewed as potentially less toxic and less expensive immune effector cell products to treat cancer patients.
Citation Format: Elizabeth J. Shpall. The future of CAR therapies [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr IA13.
Abstract IA17: The role of the senescence-associated secretory phenotype in cancer
Authors: Patel Rupesh S. , Romero Rodrigo , Liang Anthony C. , Watson Emma V. , Burger Megan , Westcott Peter M.K. , Mercer Kim L. , Bronson Roderick T. , Wooten Eric C. , Bhutkar Arjun , Jacks Tyler , Elledge Stephen J. 
Published: February 2021

Abstract
Cellular senescence is a stress-activated differentiation pathway that causes proliferation arrest governed by two powerful tumor suppressor pathways, USP28-TP53-CDKN1A and CDKN2A-RB. Senescent cells exhibit a pro-inflammatory secretory program termed the senescence-associated secretory phenotype (SASP) that is composed of chemokines, cytokines, growth factors, and proteases. SASP induction is independent of TP53 and RB function and its role in cancer has not been fully elucidated. We genetically targeted the master regulator of SASP, GATA4, and found that SASP functions as a non-cell autonomous tumor suppressor mechanism. We show that SASP is tumor suppressive in mouse models of cancer using both deletion and overexpression contexts. SASP-dependent tumor suppression requires the immune system, specifically CD8 cytotoxic T cells, to suppress tumor growth. Human tumors deficient in GATA4 have reduced lymphocyte infiltrates, indicating that human cancers may avoid immune infiltration by limiting SASP.
Citation Format: Rupesh S. Patel, Rodrigo Romero, Anthony C. Liang, Emma V. Watson, Megan Burger, Peter M.K. Westcott, Kim L. Mercer, Roderick T. Bronson, Eric C. Wooten, Arjun Bhutkar, Tyler Jacks, Stephen J. Elledge. The role of the senescence-associated secretory phenotype in cancer [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr IA17.
Abstract PO009: Epigenetic silencing by SETDB1 represses tumor-cell intrinsic immunogenicity
Authors: Wu Jingyi , Iracheta-Vellve Arvin , Patti James , Hsu Jeffrey , Davis Thomas , Dele-Oni Deborah , Du Peter , Ishizuka Jeffrey , Kim Sarah , Klaeger Susan , Knudsen Nelson , Miller Brian , Nguyen Tung , Robitschek Emily , Schneider Emily , Zimmer Margaret , Jaffe Jacob , Doench John , Haining W. Nicholas , Yates Kathleen , Manguso Robert , Bernstein Bradley , Griffin Gabriel K. 
Published: February 2021

Abstract
Epigenetic alterations are defining features of many tumor types and have recently been implicated in tumor immunity. However, the epigenetic mechanisms that mediate immune sensitivity or resistance in cancer cells are poorly characterized. To systematically identify epigenetic regulators of immune evasion in cancer, we performed in vivo loss of function CRISPR screens against 936 chromatin regulator genes in syngeneic murine tumor models treated with immune checkpoint blockade. These screens identified SETDB1, an H3K9-methyltransferase, and associated members of the HUSH and KAP1 complexes as intrinsic mediators of immune evasion in cancer cells. We also found that amplification of SETDB1 (1q21) in certain human tumors is associated with immune exclusion and resistance to immune checkpoint blockade. Mechanistically, we find that SETDB1 targets broad domains, hundreds of kilobases in size, that are predominantly located within the open genome compartment “A” (i.e., euchromatin). These SETDB1 domains show strong enrichment for transposable elements (TEs) of the LTR family, and gene loci that arose through segmental duplication events, a key driver of mammalian genome evolution. Setdb1 KO derepresses latent regulatory elements at TEs within these regions and leads to the transcriptional up-regulation of nearby immune genes, including canonical stimulatory ligands of the NKG2D receptor. SETDB1 loss also triggers the activation of hundreds of TEs with the potential to encode retroviral proteins (Gag, Pol, Env), and promotes immune responses dependent on CD8+ T cells and tumor expression of MHC Class I. Our study establishes SETDB1 as an epigenetic checkpoint that represses intrinsic immunogenicity in cancer cells, and thus represents a novel target to enhance the efficacy and scope of immunotherapy.
Citation Format: Jingyi Wu, Arvin Iracheta-Vellve, James Patti, Jeffrey Hsu, Thomas Davis, Deborah Dele-Oni, Peter Du, Jeffrey Ishizuka, Sarah Kim, Susan Klaeger, Nelson Knudsen, Brian Miller, Tung Nguyen, Emily Robitschek, Emily Schneider, Margaret Zimmer, Jacob Jaffe, John Doench, W. Nicholas Haining, Kathleen Yates, Robert Manguso, Bradley Bernstein, Gabriel K. Griffin. Epigenetic silencing by SETDB1 represses tumor-cell intrinsic immunogenicity [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO009.