bluuebunny/crossref_metadata_2025_split huggingface dataset:
Matricellular Protein CCN1 Activates a Proinflammatory Genetic Program in Murine Macrophages
Authors: Bai Tao , Chen Chih-Chiun , Lau Lester F. 
Published: February 2010

Abstract
CCN1 (CYR61) is a matricellular protein that is highly expressed at sites of inflammation and wound repair. In these contexts, CCN1 can modify the activities of specific cytokines, enabling TNF-α to be cytotoxic without blocking NF-κB activity and enhancing the apoptotic activity of Fas ligand and TRAIL. In this paper, we show that CCN1 supports the adhesion of macrophages through integrin αMβ2 and syndecan-4, activates NFκB-mediated transcription, and induces a proinflammatory genetic program characteristic of classically activated M1 macrophages that participates in Th1 responses. The effects of CCN1 include upregulation of cytokines (TNF-α, IL-1α, IL-1β, IL-6, and IL-12b), chemokines (MIP-1α; MCP-3; growth-related oncogenes 1 and 2; and inflammatory protein 10), and regulators of oxidative stress and complement (inducible NO synthase and C3) and downregulation of specific receptors (TLR4 and IL-10Rβ) and anti-inflammatory factors (TGF-β1). CCN1 regulates this genetic program through at least two distinct mechanisms: an immediate-early response resulting from direct activation of NF-κB by CCN1, leading to the synthesis of cytokines including TNF-α and inflammatory protein 10; and a delayed response resulting from CCN1-induced TNF-α, which acts as an autocrine/paracrine mediator to activate the expression of other cytokines including IL-1β and IL-6. These results identify CCN1 as a novel component of the extracellular matrix that activates proinflammatory genes in macrophages, implicating its role in regulating macrophage function during inflammation.
Immunological Property of Antibodies against N-Glycolylneuraminic Acid Epitopes in Cytidine Monophospho–N-Acetylneuraminic Acid Hydroxylase-Deficient Mice
Authors: Tahara Hiroyuki , Ide Kentaro , Basnet Nabin Bahadur , Tanaka Yuka , Matsuda Haruo , Takematsu Hiromu , Kozutsumi Yasunori , Ohdan Hideki 
Published: February 2010

Abstract
The generation of pigs devoid of Galα1,3Galβ1,4GlcNAc (Gal) residues has stimulated interest in non-Gal Ags as potentially important targets for Ab binding leading to rejection of pig organ xenografts in humans. Although N-glycolylneuraminic acid (NeuGc) epitopes, which are widely expressed on the endothelial cells of all mammals except humans, are likely targets of anti–non-Gal Abs, this aspect has not been investigated intensively owing to the absence of an appropriate animal model. In this study, we used CMAH−/− mice, which are completely deficient in NeuGc and thus produce anti-NeuGc Abs. Sera obtained from CMAH−/− mice and healthy human volunteers having anti-NeuGc Abs initiated complement-mediated lysis against CMAH+/+ cells in vitro. The cytotoxic activity of anti-NeuGc Abs was also determined in vivo (i.e., NeuGc-expressing CMAH+/+ mouse splenocytes that had been i.v. injected were completely eliminated in syngeneic CMAH−/− mice). CMAH−/− mice rejected the islets transplanted from syngeneic CMAH+/+ mice. Thus, the anti-NeuGc Ab-mediated response may be crucially involved in xenograft loss. This is the first direct demonstration of the immunogenic property of NeuGc determinants as targets of the corresponding Abs in CMAH+/+-to-CMAH−/− transplantation setting.
Substrain Differences Reveal Novel Disease-Modifying Gene Candidates That Alter the Clinical Course of a Rodent Model of Multiple Sclerosis
Authors: deLuca Leslie E. Summers , Pikor Natalia B. , O’Leary Jennifer , Galicia-Rosas Georgina , Ward Lesley A. , Defreitas Dustin , Finlay Trisha M. , Ousman Shalina S. , Osborne Lucy R. , Gommerman Jennifer L. 
Published: February 2010

Abstract
Experimental autoimmune encephalomyelitis (EAE) is a rodent model of multiple sclerosis that is executed in animals by immunization with myelin Ag in adjuvant. The SJL/J autoimmune-prone strain of mouse has been used to model relapsing–remitting multiple sclerosis. However, significant variations in peak scores, timing of onset, and incidence are observed among laboratories, with the postacute (relapse) phase of the disease exhibiting significant inconsistency. We characterized two substrains of SJL/J mice that exhibit profoundly different EAE disease parameters. Induction of EAE in the first SJL/J substrain resulted in many cases of chronic EAE that was dominated by an aggressive B cell response to the immunizing Ag and to endogenous CNS Ags. In contrast, the other SJL/J substrain exhibited a relapsing–remitting form of EAE concomitant with an elevated number of cytokine-producing CD4+ T cells in the CNS. Exploiting these interstrain differences, we performed a genome-wide copy number analysis on the two disparate SJL/J substrains and discovered numerous gene-dosage differences. In particular, one inflammation-associated gene, Naip1, was present at a higher copy number in the SJL/J substrain that exhibited relapsing–remitting EAE. These results demonstrate that substrain differences, perhaps at the level of genomic copy number, can account for variability in the postacute phase of EAE and may drive chronic versus relapsing disease.
Intense Antiextracellular Adaptive Immune Response to Human Cytomegalovirus in Very Old Subjects with Impaired Health and Cognitive and Functional Status
Authors: Vescovini Rosanna , Biasini Claudia , Telera Anna Rita , Basaglia Manuela , Stella Adriano , Magalini Francesca , Bucci Laura , Monti Daniela , Lazzarotto Tiziana , Dal Monte Paola , Pedrazzoni Mario , Medici Maria Cristina , Chezzi Carlo , Franceschi Claudio , Fagnoni Francesco F. , Sansoni Paolo 
Published: February 2010

Abstract
Human aging is characterized by expanded and altered adaptive immune responses to human CMV (HCMV). It is unclear whether this expansion has its origins in age-related homeostatic disturbances or viral reactivation, whether anti-CMV immune surveillance may still be effective, and what are the consequences of this expanded immune response for health and longevity. We conducted an observational cross-sectional study in groups of HCMV-seropositive subjects aged ≥65 y of variable health status to compare the intensity of Ab responses against HCMV with those against EBV and with CD4+ and CD8+ T cell proinflammatory effector responses directed to HCMV-derived pp65 and immediate-early protein 1 synthetic peptides. Ab responses to HCMV, but not to EBV, and anti-HCMV CD4+, but not CD8+, T cell responses were more intense in elderly subjects aged ≥85 y in poor health and were inversely correlated with markers of functional activity and cognitive function. Therefore, humoral and CD4+ T cell anti-HCMV responses were specifically intensified in advanced aging associated with comorbidity and cognitive and functional impairments. Such a distinctive pattern of adaptive immunity indicates that immune responses targeting the extracellular phase of HCMV are increased in these elderly subjects and could represent an indirect effect of localized and undetectable HCMV reactivation. This study demonstrates that the oldest subjects in poor health with physical and mental impairment express intense functional immune responses to extracellular HCMV and suggests that they may be at risk for direct pathogenic effects by HCMV reactivation as well as indirect pathogenic effects linked to proinflammatory anti-HCMV effector responses.
Cutting Edge: Polyinosinic:Polycytidylic Acid Boosts the Generation of Memory CD8 T Cells through Melanoma Differentiation-Associated Protein 5 Expressed in Stromal Cells
Authors: Wang Yaming , Cella Marina , Gilfillan Susan , Colonna Marco 
Published: February 2010

Abstract
Polyinosinic:polycytidylic acid (poly I:C), a synthetic analog of double-stranded viral RNA, serves as a potent adjuvant for vaccination against soluble proteins, pathogens, and tumors. Poly I:C is sensed by both TLR3 in the endosomes and melanoma differentiation-associated protein 5 (MDA5) in the cytoplasm. Although it is known that TLR3 is required for cross-priming of CD8 T cells specific for viral Ags, the role of MDA5 in inducing CD8 T cell responses is still unclear. In this study, we demonstrate that in mice lacking MDA5, the majority of CD8 T cells do not survive after primary immunization with poly I:C and Ag, impairing memory response to subsequent Ag challenge. Furthermore, bone marrow chimera experiments revealed that MDA5 expression in radiation-resistant stromal cells, but not in radiation-sensitive hematopoietic cells, is essential for establishing CD8 T cell memory. We conclude that MDA5 and TLR3 mediate substantially distinct yet complementary functions during poly I:C-mediated activation of Ag-specific CD8 T cell responses.
The Major Locus for Mouse Adenovirus Susceptibility Maps to Genes of the Hematopoietic Cell Surface-Expressed LY6 Family
Authors: Spindler Katherine R. , Welton Amanda R. , Lim Efrem S. , Duvvuru Suman , Althaus Irene W. , Imperiale Jennifer E. , Daoud Adam I. , Chesler Elissa J. 
Published: February 2010

Abstract
Susceptibility to mouse adenovirus type 1 is associated with the major quantitative trait locus Msq1. Msq1 was originally mapped to a 13-Mb region of mouse chromosome (Chr) 15 in crosses between SJL/J and BALB/cJ inbred mice. We have now narrowed Msq1 to a 0.75-Mb interval from 74.68 to 75.43 Mb, defined by two anonymous markers, rs8259436 and D15Spn14, using data from 1396 backcross mice. The critical interval includes 14 Ly6 or Ly6-related genes, including Ly6a (encoding Sca-1/TAP), Ly6e (Sca-2/Tsa1), Ly6g (Gr-1), and gpihbp1 (GPI-anchored high-density lipoprotein–binding protein 1), as well as the gene encoding an aldosterone synthase (Cyp11b2). The Ly6 family members are attractive candidates for virus susceptibility genes because their products are GPI-anchored membrane proteins expressed on lymphoid and myeloid cells, with proposed functions in cell adhesion and cell signaling. To determine interstrain variation in susceptibility and produce additional resources for cloning Msq1, we assayed the susceptibility phenotype of four previously untested inbred mouse strains. Susceptibility of strain 129S6/SvEvTac was subsequently localized to the Ly6 complex region, using polymorphic genetic markers on Chr 15 in a population of 271 (129S6/SvEvTac × BALB/cJ)F1 × BALB/cJ backcross mice. We identified a major 129S6/SvEvTac susceptibility allele, Msq1129S6, on Chr 15 in the same region as Msq1SJL. The results indicate that a major host factor in mouse adenovirus type 1 susceptibility is likely to be a member of the Ly6 gene family.
Antiviral Response Dictated by Choreographed Cascade of Transcription Factors
Authors: Zaslavsky Elena , Hershberg Uri , Seto Jeremy , Pham Alissa M. , Marquez Susanna , Duke Jamie L. , Wetmur James G. , tenOever Benjamin R. , Sealfon Stuart C. , Kleinstein Steven H. 
Published: February 2010

AbstractThe dendritic cell (DC) is a master regulator of immune responses. Pathogenic viruses subvert normal immune function in DCs through the expression of immune antagonists. Understanding how these antagonists interact with the host immune system requires knowledge of the underlying genetic regulatory network that operates during an uninhibited antiviral response. To isolate and identify this network, we studied DCs infected with Newcastle disease virus, which is able to stimulate innate immunity and DC maturation through activation of RIG-I signaling, but lacks the ability to evade the human IFN response. To analyze this experimental model, we developed a new approach integrating genome-wide expression kinetics and time-dependent promoter analysis. We found that the genetic program underlying the antiviral cell-state transition during the first 18 h postinfection could be explained by a single convergent regulatory network. Gene expression changes were driven by a stepwise multifactor cascading control mechanism, where the specific transcription factors controlling expression changed over time. Within this network, most individual genes were regulated by multiple factors, indicating robustness against virus-encoded immune evasion genes. In addition to effectively recapitulating current biological knowledge, we predicted, and validated experimentally, antiviral roles for several novel transcription factors. More generally, our results show how a genetic program can be temporally controlled through a single regulatory network to achieve the large-scale genetic reprogramming characteristic of cell-state transitions.
Transfusion of Nonobese Diabetic Mice with Allogeneic Newborn Blood Ameliorates Autoimmune Diabetes and Modifies the Expression of Selected Immune Response Genes
Authors: Jayaraman Sundararajan , Patel Tejas , Patel Vasu , Ajani Shahnaz , Garza Rebecca , Jayaraman Arathi , Kwon Sung , Singh Rajvir , Rondelli Damiano , Prabhakar Bellur S. , Holterman Mark 
Published: February 2010

Abstract
Although allogeneic bone marrow transplantation has been shown to prevent autoimmune diabetes in heavily irradiated nonobese diabetic (NOD) mice, a similar procedure is not suitable for the treatment of patients with type 1 diabetes because of associated severe side effects. Therefore, we evaluated whether mouse newborn blood (NBB), equivalent to human umbilical cord blood, could be used for diabetes prevention without recipient preconditioning. To test this hypothesis, unconditioned, prediabetic female NOD mice were given a single injection of whole NBB derived from the allogeneic diabetes-resistant mouse strain C57BL/6. Transfusion of allogeneic NBB but not adult blood prevented diabetes incidence in a majority of treated mice for a prolonged period of time. This was accompanied by the release of insulin in response to a challenge with glucose. Invasive cellular infiltration of islets was also substantially reduced in these mice. Although NBB transfusion induced a low level of hematopoietic microchimerism, it did not strictly correlate with amelioration of diabetes. Induction of genes implicated in diabetes, such as Il18, Tnfa, and Inos but not Il4, Il17 or Ifng, was repressed in splenocytes derived from protected mice. Notably, expression of the transcription factor Tbet/Tbx21 but not Gata3 or Rorgt was upregulated in protected mice. These data indicate that allogeneic NBB transfusion can prevent diabetes in NOD mice associated with modulation of selected cytokine genes implicated in diabetes manifestation. The data presented in this study provide the proof of principle for the utility of allogeneic umbilical cord blood transfusion to treat patients with autoimmune diabetes.
Cutting Edge: Mincle Is Essential for Recognition and Adjuvanticity of the Mycobacterial Cord Factor and its Synthetic Analog Trehalose-Dibehenate
Authors: Schoenen Hanne , Bodendorfer Barbara , Hitchens Kelly , Manzanero Silvia , Werninghaus Kerstin , Nimmerjahn Falk , Agger Else Marie , Stenger Steffen , Andersen Peter , Ruland Jürgen , Brown Gordon D. , Wells Christine , Lang Roland 
Published: February 2010

Abstract
The mycobacterial cord factor trehalose-6,6-dimycolate (TDM) and its synthetic analog trehalose-6,6-dibehenate (TDB) are potent adjuvants for Th1/Th17 vaccination that activate Syk-Card9 signaling in APCs. In this study, we have further investigated the molecular mechanism of innate immune activation by TDM and TDB. The Syk-coupling adapter protein FcRγ was essential for macrophage activation and Th17 adjuvanticity. The FcRγ-associated C-type lectin receptor Mincle was expressed in macrophages and upregulated by TDM and TDB. Recombinant Mincle-Fc fusion protein specifically bound to the glycolipids. Genetic ablation of Mincle abolished TDM/TDB-induced macrophage activation and induction of T cell immune responses to a tuberculosis subunit vaccine. Macrophages lacking Mincle or FcRγ were impaired in the inflammatory response to Mycobacterium bovis bacillus Calmette-Guérin. These results establish that Mincle is a key receptor for the mycobacterial cord factor and controls the Th1/Th17 adjuvanticity of TDM and TDB.
Illness Behavior
Authors: Ensalada Leon , Kertay Les 
Published: May 2024

Abstract
Illness behavior refers to the ways in which given symptoms may be perceived, evaluated, and acted on by different persons and can be conscious or unconscious (the latter means unnoticeable and refers to mental processes and content that are significant in determining behavior but of which the person is unaware). Further, consciousness of actions (voluntariness) and consciousness of motives (intentionality) are not necessarily associated. Illness behavior can be learned and reinforced and is a potential confounder in the association between illness or injury and impairment or disability. Illness behavior is not an impairing condition according to the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), and a table in the article describes the characteristics of the symptom magnification syndrome and other related conditions. Three diagnoses—somatic symptom disorders, illness anxiety disorder, and conversion disorder—possibly are ratable using the AMA Guides. Unsupported and insupportable conclusions regarding symptom exaggeration represent substandard practice because of the importance of such conclusions to the disposition of patients who present for assessment of impairment or disability. Similarly, failure to note and account for illness behavior and symptom exaggeration also represent substandard practice because the goal in impairment ratings is to note and account for all evidence related to the impairment, including the extent of illness behaviors.
A Semi‐Interpenetrating Poly(Ionic Liquid) Network‐Driven Low Hysteresis and Transparent Hydrogel as a Self‐Powered Multifunctional Sensor
Authors: Han Shaowei , Hu Yongkang , Wei Jia , Li Songwei , Yang Peipei , Mi Haoyang , Liu Chuntai , Shen Changyu 
Published: May 2024

AbstractConductive hydrogels are gaining significant attention as promising candidates for the fabrication materials for flexible electronics. Nevertheless, improving the tensile properties, hysteresis, durability, adhesion, and electrochemical properties of these hydrogels remains challenging. This work reports the development of a novel semi‐interpenetrating network poly(ionic liquid) hydrogel named PATV, via the in situ polymerization of acrylamide, N‐[Tris(hydroxymethyl)methyl] acrylamide, and 1‐vinyl‐3‐butylimidazolium tetrafluoroborate. The density functional theory calculations reveal that the poly(ionic liquid) in the hydrogel network acts as physical cross–linking points to construct hydrogen‐bond networks. Furthermore, the hydrogen‐bond networks dissipate energy efficiently and quickly, and thus stress concentration and hysteresis are avoided. The prepared hydrogel has a low hysteresis (9%), high tensile properties (900%), fast response (180 ms), high sensitivity (gauge factor = 10.4, pressure sensitivity = 0.14 kPa−1), and wide sensing range (tensile range: 1–600%, compression range: 0.1–20 kPa). A multifunctional sensor designed based on the designed hydrogel enables real‐time, rapid, and stable response‐ability for the detection of human movement, facial expression recognition, pronunciation, pulse, handwriting, and Morse code encryption. Furthermore, the assembled triboelectric nanogenerator displays an excellent energy harvesting capability, thus highlighting its potential application in self‐powered flexible wearable electronic devices.
Nitrogen‐Rich Carbon Dot‐Mediated n→π* Electronic Transition in Carbon Nitride for Superior Photocatalytic Hydrogen Peroxide Production
Authors: Guo Huazhang , Zhou Li , Huang Kai , Li Yongqiang , Hou Weidong , Liao Huange , Lian Cheng , Yang Siwei , Wu Deli , Lei Zhendong , Liu Zheng , Wang Liang 
Published: May 2024

AbstractSolar‐driven synthesis of hydrogen peroxide (H2O2) through photocatalysis stands out as a promising avenue for sustainable energy generation, marked by environmental friendliness and industrial feasibility. However, the inherent limitations of carbon nitride (CN) in photocatalytic H2O2 production significantly impede their performance. Herein, a novel 0D/2D carbon dots‐modified CN nanosheet heterojunction (CDsMCN) is introduced, synthesized through a hydrothermal‐calcination tandem strategy induced by CDs derived from melamine. This innovative technique enhances the n→π* electronic transition in CDsMCN, accelerating the separation efficiency of electron‐hole pairs, boosting oxygen adsorption, and promoting a highly selective 2e− ORR. Comparative to pristine CN, CDs10MCN exhibited a remarkable tenfold increase in H2O2 production, reaching an impressive 1.48 mmol L−1. Furthermore, CDs10MCN demonstrates exceptional stability, maintaining its catalytic efficiency at the initial level over four consecutive cycles. The notable achievement of a molar selectivity of H2O2 ≈80% at an onset potential of 0.6 V (vs RHE) underscores its exceptional ability to produce the desired product selectively. Advanced in situ characterization together with DFT calculations revealed that the ultrathin CDs10MCN nanosheet heterojunction with enhanced n→π* electronic transition improves its optical properties, reduces bandgap, facilitates fast charge migration, and increases photocatalytic H2O2 performance, thereby serving as a promising candidate for advanced catalytic applications.
An Efficient Fiber Gel Dye‐Sensitized Solar Cell with Stable Interlaced Interfaces
Authors: Kang Xinyue , Song Jiatian , Liu Jiuzhou , Cao Siwei , Lin Zhengmeng , Jiang Hongyu , Yang Yiqing , Cheng Xiangran , Ai Yulu , Sun Xuemei , Zeng Kaiwen , Zhu Zhengfeng , Peng Huisheng 
Published: May 2024

AbstractFiber gel dye‐sensitized solar cells (FGDSCs) are recognized as an effective solution for high‐performance, durable and safe wearable power supply. However, poor and unstable interfaces between fiber electrodes and gel electrolytes are bottleneck problems that have restricted the photovoltaic performances of FGDSCs and their stabilities during deformations. Here, an FGDSC with stable interlaced interfaces is designed by incorporating polymerized gel electrolyte into the aligned channels in fiber electrodes and the gaps between photoanode and counter electrode in situ. The interlaced structure of gel electrolyte in FGDSC improves the interfacial stability and provided stable channels for rapid ion diffusions, offering efficient charge transports at interfaces. The resulting FGDSC thus produced a high power conversion efficiency of 7.95%, and it is further maintained by over 90% after bending for 5000 cycles. These FGDSCs can be integrated with fiber batteries as a self‐charging power system, demonstrating an effective power solution for wearables.
Novel Penetrated Nucleation Mechanism for Controlled Synthesis of 2D Materials on Metal Substrates
Authors: Xu Shaogang , He Changchun , Yan Feini , He Chao , Dong Xingxing , Yang Xiaobao , Xu Hu 
Published: May 2024

Abstract2D materials have attracted considerable attention in the past decades for their unique properties, making the understanding of their nucleation process key to effective synthesis. Traditional explanations of thin‐film growth, focusing on the competition between atom interactions at the interface and within layers, often fall short of explaining real experimental results. Herein, a penetrated nucleation mechanism is proposed for 2D materials growth on metal substrates, taking into account the role of metal substrate atoms. This approach leads to a better understanding of how the surface shape evolves in two specific ways during growth in real experimental findings. Supported by detailed first‐principles simulations of boron on metal substrates and thermodynamic analyses of other studies involving metals and nonmetals, the above‐proposed mechanism is validated. Moreover, a broad strategy for growing large‐scale 2D materials on metal surfaces without creating undesired alloy layers is also presented, by adjusting the interfacial interactions by surface passivation, validated by existing experiments.