gebhart/patrepeval huggingface dataset:
mE10, a Novel Caspase Recruitment Domain-containing Proapoptotic Molecule (1999)

Apoptotic signaling is mediated by homophilic interactions between conserved domains present in components of the death pathway. The death domain, death effector domain, and caspase recruitment domain (CARD) are examples of such interaction motifs. We have identified a novel mammalian CARD-containing adaptor molecule termed mE10 (mammalian E10). The N-terminal CARD of mE10 exhibits significant homology (47% identity and 64% similarity) to the CARD of a gene from Equine Herpesvirus type 2. The C-terminal region is unique. Overexpression of mE10 in MCF-7 human breast carcinoma cells induces apoptosis. Mutational analysis indicates that CARD-mediated mE10 oligomerization is essential for killing activity. The C terminus of mE10 bound to the zymogen form of caspase-9 and promoted its processing to the active dimeric species. Taken together, these data suggest a model where autoproteolytic activation of pro-caspase-9 is mediated by mE10-induced oligomerization.
TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth (2017)

Infection is the most common cause of mortality in early life, and immunization is the most promising biomedical intervention to reduce this burden. However, newborns fail to respond optimally to most vaccines. Adjuvantation is a key approach to enhancing vaccine immunogenicity, but responses of human newborn leukocytes to most candidate adjuvants, including most TLR agonists, are functionally distinct. Herein, we demonstrate that 3M-052 is a locally acting lipidated imidazoquinoline TLR7/8 agonist adjuvant in mice, which, when properly formulated, can induce robust Th1 cytokine production by human newborn leukocytes in vitro, both alone and in synergy with the alum-adjuvanted pneumococcal conjugate vaccine 13 (PCV13). When admixed with PCV13 and administered i.m. on the first day of life to rhesus macaques, 3M-052 dramatically enhanced generation of Th1 CRM-197-specific neonatal CD4<sup>+</sup> cells, activation of newborn and infant <i>Streptococcus pneumoniae</i> polysaccharide-specific (PnPS-specific) B cells as well as serotype-specific antibody titers, and opsonophagocytic killing. Remarkably, a single dose at birth of PCV13 plus 0.1 mg/kg 3M-052 induced PnPS-specific IgG responses that were approximately 10-100 times greater than a single birth dose of PCV13 alone, rapidly exceeding the serologic correlate of protection, as early as 28 days of life. This potent immunization strategy, potentially effective with one birth dose, could represent a new paradigm in early life vaccine development.
Regulation of Found in Inflammatory Zone 1 Expression in Bleomycin-Induced Lung Fibrosis: Role of IL-4/IL-13 and Mediation via STAT-6 (2004)

Found in inflammatory zone (FIZZ)1, also known as resistin-like molecule alpha, belongs to a novel class of cysteine-rich secreted protein family, named FIZZ/resistin-like molecule, with unique tissue expression patterns. FIZZ1 is induced in alveolar type II epithelial cells (AECs) in bleomycin (BLM)-induced lung fibrosis, and found to induce myofibroblast differentiation in vitro. The objective of this study was to elucidate the regulation of AEC FIZZ1 expression in pulmonary fibrosis. AECs were isolated from rat lungs and the effects of a number of cytokines on FIZZ1 expression were evaluated by RT-PCR. Of all cytokines examined, only IL-4 and IL-13 were effective in stimulating FIZZ1 expression in AECs. Stimulation by IL-4/IL-13 was accompanied by increases in phosphorylated STAT6 and JAK1. FIZZ1 expression was also stimulated by transfection with a STAT6 expression plasmid, but was inhibited by antisense oligonucleotides directed against STAT6. In vivo studies showed that compared with wild-type controls, both IL-4- and IL-13-deficient mice showed reduced BLM-induced lung FIZZ1 expression and fibrosis, which were essentially abolished in IL-4 and IL-13 doubly deficient mice. Furthermore, STAT6-deficient mice showed marked reduction in BLM-induced lung FIZZ1 expression. Thus, IL-4 and IL-13 are potent inducers of AEC FIZZ1 expression via STAT6 and play key roles in BLM-induced lung FIZZ1 expression and fibrosis. This represents a potential mechanism by which IL-4/IL-13 could play a role in the pathogenesis of lung fibrosis.
Xenograft Tolerance (1994)

Immunological ReviewsVolume 141, Issue 1 p. 245-276 Xenograft Tolerance Megan Sykes, Megan Sykes Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital, Harvard Medical School, MGH-East, Building 149-9019, 13th Street, Boston, MA 02129, USASearch for more papers by this authorLorri A. Lee, Lorri A. Lee Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital, Harvard Medical School, MGH-East, Building 149-9019, 13th Street, Boston, MA 02129, USASearch for more papers by this authorDavid H. Sachs, Corresponding Author David H. Sachs Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital, Harvard Medical School, MGH-East, Building 149-9019, 13th Street, Boston, MA 02129, USAshould be addressed to: David H. Sachs, M.D., Transplantation Biology Research Center, Massachusetts General Hospital, MGH-East, Building 149-9019, 13th Street, Boston, MA 02129, U.S.A. Phone: 617-726-4065, Fax: 617-726-4067.Search for more papers by this author Megan Sykes, Megan Sykes Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital, Harvard Medical School, MGH-East, Building 149-9019, 13th Street, Boston, MA 02129, USASearch for more papers by this authorLorri A. Lee, Lorri A. Lee Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital, Harvard Medical School, MGH-East, Building 149-9019, 13th Street, Boston, MA 02129, USASearch for more papers by this authorDavid H. Sachs, Corresponding Author David H. Sachs Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital, Harvard Medical School, MGH-East, Building 149-9019, 13th Street, Boston, MA 02129, USAshould be addressed to: David H. Sachs, M.D., Transplantation Biology Research Center, Massachusetts General Hospital, MGH-East, Building 149-9019, 13th Street, Boston, MA 02129, U.S.A. Phone: 617-726-4065, Fax: 617-726-4067.Search for more papers by this author First published: October 1994 https://doi.org/10.1111/j.1600-065X.1994.tb00880.xCitations: 47AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume141, Issue1October 1994Pages 245-276 RelatedInformation
Platelet Factor-4 Inhibits the Mitogenic Activity of VEGF121 and VEGF165 Using Several Concurrent Mechanisms (1995)

The 121-amino acid form of vascular endothelial growth factor (VEGF121) and the 165-amino acid form (VEGF165) are mitogenic for vascular endothelial cells and induce angiogenesis in vivo. VEGF165 possesses a heparin binding ability and in the absence of heparin-like molecules does not bind efficiently to the VEGF receptors of vascular endothelial cells. The binding of 125I-VEGF165 to the VEGF receptors of endothelial cells, and the heparin-dependent binding of 125I-VEGF165 to a soluble extracellular domain of the VEGF receptor KDR/flk-1, were inhibited by the angiogenesis inhibitor platelet factor-4 (PF4). In contrast, PF4 was not able to inhibit the binding of VEGF121, a VEGF isoform which lacks a heparin binding capacity, to the VEGF receptors of the cells or to KDR/flk-1. These results indicate that PF4 may inhibit VEGF165 binding to VEGF receptors by disrupting the interaction of VEGF165 with cell surface heparan sulfates. Since PF4 mutants lacking a heparin binding ability retain their anti-angiogenic activity, alternative inhibitory mechanisms were also examined. 125I-PF4 bound with high affinity (Kd 5 x 10(-9) M) to VEGF165-coated wells. The binding of 125I-PF4 to the VEGF165-coated wells was inhibited by several types of heparin binding proteins, including unlabeled PF4 and unlabeled VEGF165. The binding was not inhibited by proteins which lack a heparin binding capacity, nor was it inhibited by VEGF121. Heparinase did not inhibit the binding of 125I-PF4 to VEGF165, indicating that heparin-like molecules are not required. These experiments suggest that PF4 can bind to heparin binding proteins such as VEGF165 leading to an inhibition of their receptor binding ability. In agreement with these results, we have observed that PF4 inhibits efficiently the VEGF165 induced proliferation of vascular endothelial cells. Unexpectedly, PF4 also inhibited efficiently the VEGF121-induced proliferation of the cells, indicating that PF4 can disrupt VEGF receptor mediated signal transduction using an unknown mechanism which does not interfere with VEGF121 binding.
The integral role of topical and oral retinoids in the early treatment of acne (2001)

This article will review the rationale for early use of topical retinoids alone or in combination with topical antimicrobials in light of the pathogenesis of microcomedones and later lesions. Knowledge of the pathogenic processes in acne vulgaris has risen dramatically over the last three decades. It is now widely accepted that acne is the result of four distinct processes: increased proliferation, cornification, and shedding of follicular epithelium; increased sebum production; colonization of the follicle with Propionibacterium acnes; and induction of inflammatory responses by bacterial antigens and cell signals. Clinical focus of disease management has shifted toward earlier treatment targeting these fundamental processes. Elimination of microcomedones, the precursor to all subsequent lesions, would optimize acne therapy by preventing the later inflammatory stages of disease. With the exception of oral isotretinoin, no single first-line agent addresses all pathogenic mechanisms. Topical retinoids have comedolytic and in some cases anti-inflammatory effects, but have no direct impact on P. acnes. Thus treatment with a combination of topical retinoid and topical antimicrobial is warranted. The former can also enhance penetration of the latter by increasing microcomedonal extrusion. In selecting a combination, one must consider efficacy, cost, and likelihood of compliance. Once thought to be effective primarily for treating comedones, topical retinoids have also been demonstrated to be effective in reducing inflammatory lesions. The activity of a topical retinoid combined with an antimicrobial agent has been shown to clear more lesions and to clear them more rapidly than antimicrobial therapy alone. Topical retinoids are also used effectively to maintain remissions.
IL-36 promotes anti-viral immunity by boosting sensitivity to IFN-α/β in IRF1 dependent and independent manners (2019)

The functions of the IL-36 cytokines remain poorly understood. We report a previously unrecognized mechanism whereby IL-36 promotes innate antiviral immunity in mouse and human models of herpes simplex virus-1 (HSV-1) infections. HSV-1 actively suppresses production of type I interferon (IFN); our data reveal that IL-36 overcomes this immune evasion strategy by increasing cellular sensitivity to IFN. IL-36β deficient mice display impaired IFN responses and poorly restrict viral replication in skin keratinocytes. In mouse and human keratinocytes IL-36 elicits an antiviral state driven by STAT1 and STAT2 via enhanced expression of IFNAR1 and IFNAR2 subunits of the type I IFN receptor. The degree of IFN regulatory factor 1 (IRF1) involvement is species dependent, with IRF1 playing a more prominent role in human cells. Similar mechanisms are activated by IL-1. Overall, IL-36 acts as an antiviral cytokine by potentiating type I IFN signaling and thereby upholds immune responses to viruses that limit the production of IFNs.
Anti-tumor Immunity and Mechanism of Immunosuppression Mediated by Tumor Cells: Role of Tumor-Derived Soluble Factors and Cytokines (2010)

The immune system plays a crucial role in the protection against tumor growth and progression. However, the activation of the immune system against the neoplastic cells does not always occur and, therefore, tumor cells are able to grow and progress continually in the host. It has now been realized that tumor cells themselves produce many of the important factors that are responsible for dismounting of effective immune response. These tumor-derived soluble factors invariably subdue the functions of almost every immune cell population. Therefore, we attempted to underline the mechanism of anti-tumor immune response and immunosuppression induced by tumor cells.
A new theory of deadlock-free adaptive routing in wormhole networks (1993)

The theoretical background for the design of deadlock-free adaptive routing algorithms for wormhole networks is developed. The author proposes some basic definitions and two theorems. These create the conditions to verify that an adaptive algorithm is deadlock-free, even when there are cycles in the channel dependency graph. Two design methodologies are also proposed. The first supplies algorithms with a high degree of freedom, without increasing the number of physical channels. The second methodology is intended for the design of fault-tolerant algorithms. Some examples are given to show the application of the methodologies. Simulations show the performance improvement that can be achieved by designing the routing algorithms with the new theory.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Characterization of the S-Phase-Specific Transcription Regulatory Elements in a DNA Replication-Independent Testis-Specific H2B (TH2B) Histone Gene (1990)

The testis-specific H2B histone (TH2B) gene is expressed in pachytene spermatocytes of meiotic prophase I during rat spermatogenesis. The TH2B RNA and histones are not synthesized in any other tissues, and the synthesis is independent of DNA replication. However, the cloned TH2B gene has two DNA sequence elements which stimulate transcription of the cloned gene in an S-phase-dependent manner when introduced into somatic cells. The factors interacting with the two elements, CCAAT at -127 base pairs and octamer ATTTGCAT at -93 base pairs, interact with each other to bring about a maximum stimulation of S-phase-dependent transcription. The level of CCAAT and octamer-binding proteins is unchanged during the cell cycle, and the S-phase-dependent transcription of TH2B and endogenous mouse H2B genes does not require synthesis of new proteins during the S phase. Cell cycle-specific posttranslational modification of regulatory proteins may be responsible for the S-phase-dependent transcription of H2B histone genes. The biological significance of the presence of S-phase-specific transcription regulatory elements in the DNA replication-independent and tissue-specific TH2B gene is not known.
Memory deficits associated with senescence: A neurophysiological and behavioral study in the rat. (1979)

Neurophysiological and behavioral measures were obtained from 32 senescent (28--34 mo) and 32 mature adult (10--16 mo) rats. Extracellularly recorded synaptic responses were obtained from electrodes chronically implanted in the fascia dentata and perforant path. The rats were first tested on a circular platform, which favored the use of spatial cues for its solution, and the senescent rats were shown to exhibit poorer memory for the rewarded place. When granule cell synaptic responses were recorded after a single session of very brief high-frequency stimulation, the amount of elevation and time course of decline were equivalent between age groups. Af ter three repetitions, however, the young rats maintained the increased synaptic strength for at least 14 days, whereas the old rats declined after the first session. The amount of synaptic enhancement was statistically correlated with the ability to perform the circular platform task both within and between groups. Furthermore, the aftereffects of the high-frequency stimulation selectively impaired the old rats' spontaneous alternation behavior on a T-maze. Certain other neurophysiological and electroencephalographic measures did not distinguish between age groups. The results are discussed in terms of the synaptic theory of memory formation and of their relevance to the aging process.
Investigating the latent polymorphism of maleic acid (2005)

The unexpected appearance of a new polymorph of maleic acid is reported and a computational study addresses the predictability of this new polymorph and future potential polymorphism.
Polymer Photovoltaic Cells with Conducting Polymer Anodes (2002)

Conducting polymer anodes for photovoltaic cells based on polyethylendioxythiophene (PEDOT) and its derivatives (see Figure) are reported. The results presented here show that it is feasible to use processable conducting (macro)molecular materials instead of indium tin oxide (ITO) for fabricating polymer photovoltaic cells, which could lead to lower cost and more mechanically flexible devices.
Design and Synthesis of a Photocleavable Fluorescent Nucleotide 3‘-O-Allyl-dGTP-PC-Bodipy-FL-510 as a Reversible Terminator for DNA Sequencing by Synthesis (2006)

DNA sequencing by synthesis (SBS) using reversible fluorescent nucleotide terminators is potentially an efficient approach to address the limitations of current DNA sequencing techniques. Here, we report the design and synthesis of a 3'-O-allyl photocleavable fluorescent nucleotide analogue, 3'-O-allyl-dGTP-PC-Bodipy-FL-510, as a reversible terminator for SBS. The nucleotide is efficiently incorporated by DNA polymerase into a growing DNA strand to terminate the polymerase reaction. After that, the fluorophore is photocleaved quantitatively by irradiation at 355 nm, and the allyl group is rapidly and efficiently removed by using a Pd-catalyzed reaction under DNA-compatible conditions to regenerate a free 3'-OH group to reinitiate the polymerase reaction. Two cycles of such steps were successfully demonstrated to sequence a homopolymeric region of a DNA template, facilitating the development of SBS as a viable approach for high-throughput DNA sequencing.
Nanoparticle-Based and Organic-Phase-Based AGET ATRP PolyHIPE Synthesis within Pickering HIPEs and Surfactant-Stabilized HIPEs (2011)

PolyHIPEs are porous polymers synthesized within high internal phase emulsions (HIPEs). Recent research has shown that the locus of conventional free radical initiation (at the oil–water interface or in the organic phase) can affect the polyHIPE’s structure and properties. This paper is the first investigation of polyHIPE synthesis using activators generated by electron transfer for atom-transfer radical polymerization (AGET ATRP). Two different types of initiators (organic-phase-based and nanoparticle-based) were used to synthesize polyHIPEs within both surfactant-stabilized HIPEs and nanoparticle-stabilized Pickering HIPEs. The type and locus of initiation affected the macromolecular structure for all the polyHIPEs. Furthermore, the initiator also affected both the porous structure and the wall structure of polyHIPEs synthesized within Pickering HIPEs. Depending upon the initiator, either a polyhedral void shape or a nanoparticle assembly at the interface could become “locked in” at the very beginning of the polymerization.
Protective cellular immunity: cytotoxic T-lymphocyte responses against dominant and recessive epitopes of influenza virus nucleoprotein induced by DNA immunization (1997)

DNA immunization offers a novel means to induce cellular immunity in a population with a heterogeneous genetic background. An immunorecessive cytotoxic T-lymphocyte (CTL) epitope in influenza virus nucleoprotein (NP), residues 218 to 226, was identified when mice were immunized with a plasmid DNA encoding a full-length mutant NP in which the anchor residues for the immunodominant NP147-155 epitope were altered. Mice immunized with wild-type or mutant NP DNA were protected from lethal cross-strain virus challenge, and the protection could be adoptively transferred by immune splenocytes, indicating the role of cell-mediated immunity in the protection. DNA immunization is capable of eliciting protective cellular immunity against both immunodominant and immunorecessive CTL epitopes in the hierarchy seen with virus infection.
New Approaches to Antiglaucoma Therapy (1997)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTNew Approaches to Antiglaucoma TherapyMichael F. SugrueView Author Information Merck Research Laboratories, West Point, Pennsylvania 19486 Cite this: J. Med. Chem. 1997, 40, 18, 2793–2809Publication Date (Web):August 29, 1997Publication History Received26 December 1996Published online29 August 1997Published inissue 1 August 1997https://pubs.acs.org/doi/10.1021/jm9608725https://doi.org/10.1021/jm9608725review-articleACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views696Altmetric-Citations71LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Agonists,Anatomy,Antagonists,Receptors,Redox reactions Get e-Alerts
CCR6 Regulates the Migration of Inflammatory and Regulatory T Cells (2008)

Th17 and regulatory T (Treg) cells play opposite roles in autoimmune diseases. However, the mechanisms underlying their proper migration to inflammatory tissues are unclear. In this study, we report that these two T cell subsets both express CCR6. CCR6 expression in Th17 cells is regulated by TGF-beta and requires two nuclear receptors, RORalpha and RORgamma. Th17 cells also express the CCR6 ligand CCL20, which is induced synergistically by TGF-beta and IL-6, which requires STAT3, RORgamma and IL-21. Th17 cells, by producing CCL20, promote migration of Th17 and Treg cells in vitro in a CCR6-dependent manner. Lack of CCR6 in Th17 cells reduces the severity of experimental autoimmune encephalomyelitis and Th17 and Treg recruitment into inflammatory tissues. Similarly, CCR6 on Treg cells is also important for their recruitment into inflammatory tissues. Our data indicate an important role of CCR6 in Treg and Th17 cell migration.