bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Transmembrane E3 Ligase GRAIL Ubiquitinates and Degrades CD83 on CD4 T Cells
Authors: Su Leon L. , Iwai Hideyuki , Lin Jack T. , Fathman C. Garrison 
Published: June 2009

Abstract
Ubiquitination of eukaryotic proteins regulates a broad range of cellular processes, including T cell activation and tolerance. We have previously demonstrated that GRAIL (gene related to anergy in lymphocytes), a transmembrane RING finger ubiquitin E3 ligase, initially described as induced during the induction of CD4 T cell anergy, is also expressed in resting CD4 T cells. In this study, we show that GRAIL can down-modulate the expression of CD83 (previously described as a cell surface marker for mature dendritic cells) on CD4 T cells. GRAIL-mediated down-modulation of CD83 is dependent on an intact GRAIL extracellular protease-associated domain and an enzymatically active cytosolic RING domain, and proceeds via the ubiquitin-dependent 26S proteosome pathway. Ubiquitin modification of lysine residues K168 and K183, but not K192, in the cytoplasmic domain of CD83 was shown to be necessary for GRAIL-mediated degradation of CD83. Reduced CD83 surface expression levels were seen both on anergized CD4 T cells and following GRAIL expression by retroviral transduction, whereas GRAIL knock-down by RNA interference in CD4 T cells resulted in elevated CD83 levels. Furthermore, CD83 expression on CD4 T cells contributes to T cell activation as a costimulatory molecule. This study supports the novel mechanism of ubiquitination by GRAIL, identifies CD83 as a substrate of GRAIL, and ascribes a role for CD83 in CD4 T cell activation.
Immunization with the DNA-Encoding N-Terminal Domain of Proteophosphoglycan of Leishmania donovani Generates Th1-Type Immunoprotective Response against Experimental Visceral Leishmaniasis
Authors: Samant Mukesh , Gupta Reema , Kumari Shraddha , Misra Pragya , Khare Prashant , Kushawaha Pramod Kumar , Sahasrabuddhe Amogh Anant , Dube Anuradha 
Published: June 2009

Abstract
Leishmania produce several types of mucin-like glycoproteins called proteophosphoglycans (PPGs) which exist as secretory as well as surface-bound forms in both promastigotes and amastigotes. The structure and function of PPGs have been reported to be species and stage specific as in the case of Leishmania major and Leishmania mexicana; there has been no such information available for Leishmania donovani. We have recently demonstrated that PPG is differentially expressed in sodium stibogluconate-sensitive and -resistant clinical isolates of L. donovani. To further elucidate the structure and function of the ppg gene of L. donovani, a partial sequence of its N-terminal domain of 1.6 kb containing the majority of antigenic determinants, was successfully cloned and expressed in prokaryotic as well as mammalian cells. We further evaluated the DNA-encoding N-terminal domain of the ppg gene as a vaccine in golden hamsters (Mesocricetus auratus) against the L. donovani challenge. The prophylactic efficacy to the tune of ∼80% was observed in vaccinated hamsters and all of them could survive beyond 6 mo after challenge. The efficacy was supported by a surge in inducible NO synthase, IFN-γ, TNF-α, and IL-12 mRNA levels along with extreme down-regulation of TGF-β, IL-4, and IL-10. A rise in the level of Leishmania-specific IgG2 was also observed which was indicative of enhanced cellular immune response. The results suggest the N-terminal domain of L. donovani ppg as a potential DNA vaccine against visceral leishmaniasis.
Follicular Dendritic Cells Activate HIV-1 Replication in Monocytes/Macrophages through a Juxtacrine Mechanism Mediated by P-Selectin Glycoprotein Ligand 1
Authors: Ohba Kenji , Ryo Akihide , Dewan Md. Zahidunnabi , Nishi Mayuko , Naito Toshio , Qi Xiaohua , Inagaki Yoshio , Nagashima Yoji , Tanaka Yuetsu , Okamoto Takashi , Terashima Kazuo , Yamamoto Naoki 
Published: June 2009

Abstract
Follicular dendritic cells (FDCs) are located in the lymphoid follicles of secondary lymphoid tissues and play a pivotal role in the selection of memory B lymphocytes within the germinal center, a major site for HIV-1 infection. Germinal centers are composed of highly activated B cells, macrophages, CD4+T cells, and FDCs. However, the physiological role of FDCs in HIV-1 replication remains largely unknown. We demonstrate in our current study that FDCs can efficiently activate HIV-1 replication in latently infected monocytic cells via an intercellular communication network mediated by the P-selectin/P-selectin glycoprotein ligand 1 (PSGL-1) interaction. Upon coculture with FDCs, HIV-1 replication was significantly induced in infected monocytic cell lines, primary monocytes, or macrophages. These cocultures were found to synergistically induce the expression of P-selectin in FDCs via NF-κB activation and its cognate receptor PSGL-1 in HIV-1-infected cells. Consistent with this observation, we find that this response is significantly blocked by antagonistic Abs against PSGL-1 and almost completely inhibited by PSGL-1 small interfering RNA. Moreover, a selective inhibitor for Syk, which is a downstream effector of PSGL-1, blocked HIV-1 replication in our cultures. We have thus elucidated a novel regulatory mechanism in which FDCs are a potent positive bystander that facilitates HIV-1 replication in adjacent infected monocytic cells via a juxtacrine signaling mechanism.
Pleiotropic Roles of S100A12 in Coronary Atherosclerotic Plaque Formation and Rupture
Authors: Goyette Jesse , Yan Wei Xing , Yamen Eric , Chung Yuen Ming , Lim Su Yin , Hsu Kenneth , Rahimi Farid , Di Girolamo Nick , Song Changjie , Jessup Wendy , Kockx Maaike , Bobryshev Yuri V. , Freedman S. Ben , Geczy Carolyn L. 
Published: June 2009

Abstract
Macrophages, cytokines, and matrix metalloproteinases (MMP) play important roles in atherogenesis. The Ca2+-binding protein S100A12 regulates monocyte migration and may contribute to atherosclerosis by inducing proinflammatory cytokines in macrophages. We found significantly higher S100A12 levels in sera from patients with coronary artery disease than controls and levels correlated positively with C-reactive protein. S100A12 was released into the coronary circulation from ruptured plaque in acute coronary syndrome, and after mechanical disruption by percutaneous coronary intervention in stable coronary artery disease. In contrast to earlier studies, S100A12 did not stimulate proinflammatory cytokine production by human monocytes or macrophages. Similarly, no induction of MMP genes was found in macrophages stimulated with S100A12. Because S100A12 binds Zn2+, we studied some functional aspects that could modulate atherogenesis. S100A12 formed a hexamer in the presence of Zn2+; a novel Ab was generated that specifically recognized this complex. By chelating Zn2+, S100A12 significantly inhibited MMP-2, MMP-9, and MMP-3, and the Zn2+-induced S100A12 complex colocalized with these in foam cells in human atheroma. S100A12 may represent a new marker of this disease and may protect advanced atherosclerotic lesions from rupture by inhibiting excessive MMP-2 and MMP-9 activities by sequestering Zn2+.
Identification of a Major Susceptibility Locus for Lethal Graft-versus-Host Disease in MHC-Matched Mice
Authors: Cao Thai M. , Lazzeroni Laura C. , Tsai Schickwann , Pang Wendy W. , Kao Amy , Camp Nicola J. , Thomas Alun , Shizuru Judith A. 
Published: June 2009

AbstractGraft-vs-host disease (GVHD) is the major cause of morbidity and mortality after allogeneic hemopoietic cell transplantation. From a genetic perspective, GVHD is a complex phenotypic trait. Although it is understood that susceptibility results from interacting polymorphisms of genes encoding histocompatibility Ags and immune regulatory molecules, a detailed and integrative understanding of the genetic background underlying GVHD remains lacking. To gain insight regarding these issues, we performed a forward genetic study. A MHC-matched mouse model was used in which irradiated recipient BALB.K and B10.BR mice demonstrate differential susceptibility to lethal GHVD when transplanted using AKR/J donors. Assessment of GVHD in (B10.BR × BALB.K)F1 mice revealed that susceptibility is a dominant trait and conferred by deleterious alleles from the BALB.K strain. To identify the alleles responsible for GVHD susceptibility, a genome-scanning approach was taken using (B10.BR × BALB.K)F1 × B10.BR backcross mice as recipients. A major susceptibility locus, termed the Gvh1 locus, was identified on chromosome 16 using linkage analysis (logarithm of the odds, 9.1). A second locus was found on chromosome 13, named Gvh2, which had additive but protective effects. Further identification of Gvh genes by positional cloning may yield new insight into genetic control mechanisms regulating GVHD and potentially reveal novel approaches for effective GVHD therapy.
Elimination of Immunodominant Epitopes from Multispecific DNA-Based Vaccines Allows Induction of CD8 T Cells That Have a Striking Antiviral Potential
Authors: Riedl Petra , Wieland Andreas , Lamberth Kasper , Buus Soren , Lemonnier Francois , Reifenberg Kurt , Reimann Jörg , Schirmbeck Reinhold 
Published: June 2009

AbstractImmunodominance limits the TCR diversity of specific antiviral CD8 T cell responses elicited by vaccination or infection. To prime multispecific T cell responses, we constructed DNA vaccines that coexpress chimeric, multidomain Ags (with CD8 T cell-defined epitopes of the hepatitis B virus (HBV) surface (S), core (C), and polymerase (Pol) proteins and/or the OVA Ag as stress protein-capturing fusion proteins. Priming of mono- or multispecific, HLA-A*0201- or Kb-restricted CD8 T cell responses by these DNA vaccines differed. Kb/OVA257–264- and Kb/S190–197-specific CD8 T cell responses did not allow priming of a Kb/C93–100-specific CD8 T cell response in mice immunized with multidomain vaccines. Tolerance to the S- Ag in transgenic Alb/HBs mice (that express large amounts of transgene-encoded S- Ag in the liver) facilitated priming of subdominant, Kb/C93–100-specific CD8 T cell immunity by multidomain Ags. The “weak” (i.e., easily suppressed) Kb/C93–100-specific CD8 T cell response was efficiently elicited by a HBV core Ag-encoding vector in 1.4HBV-Smut tg mice (that harbor a replicating HBV genome that produces HBV surface, core, and precore Ag in the liver). Kb/C93–100-specific CD8 T cells accumulated in the liver of vaccinated 1.4HBV-Smut transgenic mice where they suppressed HBV replication. Subdominant epitopes in vaccines can hence prime specific CD8 T cell immunity in a tolerogenic milieu that delivers specific antiviral effects to HBV-expressing hepatocytes.
Structural Bases for the Affinity-Driven Selection of a Public TCR against a Dominant Human Cytomegalovirus Epitope
Authors: Gras Stéphanie , Saulquin Xavier , Reiser Jean-Baptiste , Debeaupuis Emilie , Echasserieau Klara , Kissenpfennig Adrien , Legoux François , Chouquet Anne , Le Gorrec Madalen , Machillot Paul , Neveu Bérangère , Thielens Nicole , Malissen Bernard , Bonneville Marc , Housset Dominique 
Published: June 2009

Abstract
Protective T cell responses elicited along chronic human CMV (HCMV) infections are sometimes dominated by CD8 T cell clones bearing highly related or identical public TCR in unrelated individuals. To understand the principles that guide emergence of these public T cell responses, we have performed structural, biophysical, and functional analyses of an immunodominant public TCR (RA14) directed against a major HLA-A*0201-restricted HCMV Ag (pp65495–503) and selected in vivo from a diverse repertoire after chronic stimulations. Unlike the two immunodominant public TCRs crystallized so far, which focused on one peptide hotspot, the HCMV-specific RA14 TCR interacts with the full array of available peptide residues. The conservation of some peptide-MHC complex-contacting amino acids by lower-affinity TCRs suggests a shared TCR-peptide-MHC complex docking mode and supports an Ag-driven selection of optimal TCRs. Therefore, the emergence of a public TCR of an oligoclonal Ag-specific response after repeated viral stimulations is based on a receptor displaying a high structural complementarity with the entire peptide and focusing on three peptide hotspots. This highlights key parameters underlying the selection of a protective T cell response against HCMV infection, which remains a major health issue in patients undergoing bone marrow transplantation.
The Initial Phase of an Immune Response Functions to Activate Regulatory T Cells
Authors: O'Gorman William E. , Dooms Hans , Thorne Steve H. , Kuswanto Wilson F. , Simonds Erin F. , Krutzik Peter O. , Nolan Garry P. , Abbas Abul K. 
Published: June 2009

Abstract
An early reaction of CD4+ T lymphocytes to Ag is the production of cytokines, notably IL-2. To detect cytokine-dependent responses, naive Ag-specific T cells were stimulated in vivo and the presence of phosphorylated STAT5 molecules was used to identify the cell populations responding to IL-2. Within hours of T cell priming, IL-2-dependent STAT5 phosphorylation occurred primarily in Foxp3+ regulatory T cells. In contrast, the Ag-specific T cells received STAT5 signals only after repeated Ag exposure or memory differentiation. Regulatory T cells receiving IL-2 signals proliferated and developed enhanced suppressive activity. These results indicate that one of the earliest events in a T cell response is the activation of endogenous regulatory cells, potentially to prevent autoimmunity.
Downstream Signals for MyD88-Mediated Phagocytosis of Borrelia burgdorferi Can Be Initiated by TRIF and Are Dependent on PI3K
Authors: Shin Ok S. , Miller Lloyd S. , Modlin Robert L. , Akira Shizuo , Uematsu Satoshi , Hu Linden T. 
Published: June 2009

Abstract
We previously have shown that MyD88 is important for uptake of Borrelia burgdorferi by bone marrow derived macrophages (BMDMs). The mechanism by which MyD88 is involved in uptake of B. burgdorferi is currently is not well characterized. Here, we report that MyD88-mediated defect in the phagocytosis of B. burgdorferi can be complemented by TLR3/Toll/IL-1R domain-containing adaptor-inducing IFN-β (TRIF) activation in BMDMs from MyD88−/− mice. This effect of TLR3/TRIF activation was not due to its induction of type I IFNs, suggesting instead a convergence of signaling pathways downstream of MyD88 and TRIF. To characterize signaling pathways involved in MyD88-mediated phagocytosis of B. burgdorferi, BMDMs were treated with specific inhibitors of MAPK, protein kinase C, JAK/STAT, or PI3K. Only inhibition of PI3K resulted in a significant decrease of B. burgdorferi uptake. Consistent with this, B. burgdorferi activation of MyD88 or TLR3/TRIF signaling resulted in increased activity of PI3K. Additionally, association of B. burgdorferi with actin-related protein (Arp2/3) complexes, which facilitate actin rearrangements during phagocytosis, was similarly reduced in MyD88−/− BMDMs and in BMDMs treated with a PI3K inhibitor. Taken together, these findings define an essential pathway whereby downstream signals from MyD88 or TRIF converge on PI3K, which triggers actin polymerization to initiate the phagocytosis of B. burgdorferi.
Spark Plasma Sintering as a Useful Technique to the Nanostructuration of Piezo‐Ferroelectric Materials
Authors: Hungría Teresa , Galy Jean , Castro Alicia 
Published: June 2009

AbstractThis review gathers detail on the processing of piezo‐ferroelectric ceramic materials by spark plasma sintering for the first time. The results reported here clearly indicate that it is a powerful technique and opens the possibility of processing ceramics with controlled sub‐micron or even nanoscale grain sizes.
Restorable Type Conversion of Carbon Nanotube Transistor Using Pyrolytically Controlled Antioxidizing Photosynthesis Coenzyme
Authors: Kang Bo Ram , Yu Woo Jong , Kim Ki Kang , Park Hyeon Ki , Kim Soo Min , Park Yongjin , Kim Gunn , Shin Hyeon‐Jin , Kim Un Jeong , Lee Eun‐Hong , Choi Jae‐Young , Lee Young Hee 
Published: June 2009

AbstractHere, a pyrolytically controlled antioxidizing photosynthesis coenzyme, β‐Nicotinamide adenine dinucleotide, reduced dipotassium salt (NADH) for a stable n‐type dopant for carbon nanotube (CNT) transistors is proposed. A strong electron transfer from NADH, mainly nicotinamide, to CNTs takes place during pyrolysis so that not only the type conversion from p‐type to n‐type is realized with 100% of reproducibility but also the on/off ratio of the transistor is significantly improved by increasing on‐current and/or decreasing off‐current. The device was stable up to a few months with negligible current changes under ambient conditions. The n‐type characteristics were completely recovered to an initial doping level after reheat treatment of the device.
Molecular Design of Unsymmetrical Squaraine Dyes for High Efficiency Conversion of Low Energy Photons into Electrons Using TiO2 Nanocrystalline Films
Authors: Geiger Thomas , Kuster Simon , Yum Jun‐Ho , Moon Soo‐Jin , Nazeeruddin Mohammad K. , Grätzel Michael , Nüesch Frank 
Published: June 2009

AbstractAn optimized unsymmetrical squaraine dye 5‐carboxy‐2‐[[3‐[(2,3‐dihydro‐1, 1‐dimethyl‐3‐ethyl‐1H‐benzo[e]indol‐2‐ylidene)methyl]‐2‐hydroxy‐4‐oxo‐2‐cyclobuten‐1‐ylidene]methyl]‐3,3‐dimethyl‐1‐octyl‐3H‐indolium (SQ02) with carboxylic acid as anchoring group is synthesized for dye‐sensitized solar cells (DSCs). Although the π‐framework of SQ02 is insignificantly extended compared to its antecessor squaraine dye SQ01, photophysical measurements show that the new sensitizer has a much higher overall conversion efficiency η of 5.40% which is improved by 20% when compared to SQ01. UV‐vis spectroscopy, cyclic voltammetry and time dependent density functional theory calculations are accomplished to rationalize the higher conversion efficiency of SQ02. A smaller optical band gap including a higher molar absorption coefficient leads to improved light harvesting of the solar cell and a broadened photocurrent spectrum. Furthermore, all excited state orbitals relevant for the π–π* transition in SQ02 are delocalized over the carboxylic acid anchoring group, ensuring a strong electronic coupling to the conduction band of TiO2 and hence a fast electron transfer.
Self‐Assembly of a Donor‐Acceptor Dyad Across Multiple Length Scales: Functional Architectures for Organic Electronics
Authors: Mativetsky Jeffrey M. , Kastler Marcel , Savage Rebecca C. , Gentilini Desirée , Palma Matteo , Pisula Wojciech , Müllen Klaus , Samorì Paolo 
Published: June 2009

AbstractMolecular dyads based on polycyclic electron donor (D) and electron acceptor (A) units represent suitable building blocks for forming highly ordered, solution‐processable, nanosegregated D‐A domains for potential use in (opto)electronic applications. A new dyad, based on alkyl substituted hexa‐peri‐hexabenzocoronene (HBC) and perylene monoimide (PMI) separated by an ethinylene linker, is shown to have a high tendency to self‐assemble into ordered supramolecular arrangements at multiple length scales: macroscopic extruded filaments display long‐range crystalline order, nanofiber networks are produced by simple spin‐coating, and monolayers with a lamellar packing are formed by physisorption at the solution‐HOPG interface. Moreover, highly uniform mesoscopic ribbons bearing atomically flat facets and steps with single‐molecule heights self‐assemble upon solvent‐vapor annealing. Electrical measurements of HBC‐PMI films and mesoscopic ribbons in a transistor configuration exhibit ambipolar transport with well balanced p‐ and n‐type mobilities. Owing to the increased level of order at the supramolecular level, devices based on ribbons show mobility increases of more than one order of magnitude.
Brittle‐to‐Ductile Transition in Uniaxial Compression of Silicon Pillars at Room Temperature
Authors: Östlund Fredrik , Rzepiejewska‐Malyska Karolina , Leifer Klaus , Hale Lucas M. , Tang Yuye , Ballarini Roberto , Gerberich William W. , Michler Johann 
Published: June 2009

AbstractRobust nanostructures for future devices will depend increasingly on their reliability. While great strides have been achieved for precisely evaluating electronic, magnetic, photonic, elasticity and strength properties, the same levels for fracture resistance have been lacking. Additionally, one of the self‐limiting features of materials by computational design is the knowledge that the atomistic potential is an appropriate one. A key property in establishing both of these goals is an experimentally‐determined effective surface energy or the work per unit fracture area. The difficulty with this property, which depends on extended defects such as dislocations, is measuring it accurately at the sub‐micrometer scale. In this Full Paper the discovery of an interesting size effect in compression tests on silicon pillars with sub‐micrometer diameters is presented: in uniaxial compression tests, pillars having a diameter exceeding a critical value develop cracks, whereas smaller pillars show ductility comparable to that of metals. The critical diameter is between 310 and 400 nm. To explain this transition a model based on dislocation shielding is proposed. For the first time, a quantitative method for evaluating the fracture toughness of such nanostructures is developed. This leads to the ability to propose plausible mechanisms for dislocation‐mediated fracture behavior in such small volumes.
The excess burden of stroke in hospitalized adults with sickle cell disease
Authors: Strouse John J. , Jordan Lori C. , Lanzkron Sophie , Casella James F. 
Published: June 2009

AbstractThis report compares the relative rates and risk factors associated with stroke in adults versus children with sickle cell disease (SCD) in the United States over the last decade. We identified incident strokes in patients with SCD using ICD‐9 codes for acute stroke and SCD and the California Patient Discharge Databases. We estimated SCD prevalence by using the incidence of SCD at birth with adjustment for early mortality from SCD. We identified 255 acute strokes (70 primary hemorrhagic and 185 ischemic) among 69,586 hospitalizations for SCD‐related complications from 1998 to 2007. The rate of stroke in children [<18 years old (310/100,000 person‐years)] was similar to young adults [18–34 years old (360/100,000 person‐years)], but much higher in middle‐aged [35–64 years old (1,160/100,000 person‐years)] and elderly adults [≥65 years old (4,700/100,000 person‐years)]. Stroke was associated with hypertension in children and hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and renal disease in adults. Most acute strokes (75%) and in‐hospital deaths from stroke (91%) occurred in adults. Our results suggest that the rate of stroke in SCD peaks in older adults and is three‐fold higher than rates previously reported in African‐Americans of similar age (35–64 years) without SCD. Stroke in SCD is associated with several known adult risk factors for ischemic and hemorrhagic stroke. Studies for the primary and secondary prevention of stroke in adults with SCD are urgently needed. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.