363 research outputs found
Interleukin-17 and innate immunity in infections and chronic inflammation
No full textInterleukin 17 (IL-17) includes several cytokines among which IL-17A is considered as one of the major pro-inflammatory cytokine being central to the innate and adaptive immune responses. IL-17 is produced by unconventional T cells, members of innate lymphoid cells (ILCs), mast cells, as well as typical innate immune cells, such as neutrophils and macrophages located in the epithelial barriers and characterised by a rapid response to infectious agents by recruiting neutrophils as first line of defence and inducing the production of antimicrobial peptides. Th17 responses appear pivotal in chronic and acute infections by bacteria, parasites, and fungi, as well as in autoimmune and chronic inflammatory diseases, including rheumatoid arthritis, psoriasis, and psoriatic arthritis. The data discussed in this review cumulatively indicate that innate-derived IL-17 constitutes a major element in the altered immune response against self antigens or the perpetuation of inflammation, particularly at mucosal sites. New drugs targeting the IL17 pathway include brodalumab, ixekizumab, and secukinumab and their use in psoriatic disease is expected to dramatically impact our approach to this systemic condition
Hyper velocity impact studies simulating debris collision on composites material
No full textThis paper describes the hyper velocity impact test to composite material. The composite material is already adopted as a structural material of many space craft. On the other hand, there is little debris collision data to composites material. Then, the hyper velocity collision experiment to the board of composite material was conducted by making board thickness, diameter and velocity of projectile into parameter. While the fracture situation by collision, internal damage, and residual compression strength are measured, since we acquired new knowledge, we report the relation between collision energy and damaged area
Using a sport event to create a sense of community: Charity sport event manager perspectives
No full textCharity sport events not only involve completing the activity, but also the opportunity to bring people together. A variety of research has examined charity sport events’ capacity to foster a sense of community from the participant point of view. The current research examines sense of community within charity sport events from the event management perspective and advances the following research question: What do charity sport event managers feel they have put in place to create sense of community among participants? To address this research question, qualitative data were collected via interviews with 15 charity sport event managers in Japan. An interview guide comprised of six demographic questions, along with nine questions based upon the sense of community in sport framework was utilized. Five themes were identified within the interviews: charitable contribution, soliciting feedback from participants, interactive event environment, supplementary activities, and lack of competition. Two themes from the sense of community in sport framework that did not emerge across the interviews underscore opportunity for event managers to leverage mobile applications and online discussion forums to engage participant’s shared interest in sport, as well as enlist leaders among event participants to serve as advocates. Based upon the current results, future research can include managers from the designated charities aligned with events to assess whether the sense of community created within these events leads to long-term benefits for the organisation.Full Tex
Supplemental Material, DS1_VET_10.1177_0300985818758471 - Accumulation of Laforin and Other Related Proteins in Canine Lafora Disease With <i>EPM2B</i> Repeat Expansion
No full textSupplemental Material, DS1_VET_10.1177_0300985818758471 for Accumulation of Laforin and Other Related Proteins in Canine Lafora Disease With EPM2B Repeat Expansion by James K. Chambers, Atigan Thongtharb, Takanori Shiga, Daigo Azakami, Miyoko Saito, Masumi Sato, Motoji Morozumi, Hiroyuki Nakayama, and Kazuyuki Uchida in Veterinary Pathology</p
Pentraxins in the activation and regulation of innate immunity
No full textHumoral fluid phase pattern recognition molecules (PRMs) are a key component of the activation and regulation of innate immunity. Humoral PRMs are diverse. We focused on the long pentraxin PTX3 as a paradigmatic example of fluid phase PRMs. PTX3 acts as a functional ancestor of antibodies and plays a non-redundant role in resistance against selected microbes in mouse and man and in the regulation of inflammation. This molecule interacts with complement components, thus modulating complement activation. In particular, PTX3 regulates complement-driven macrophage-mediated tumor progression, acting as an extrinsic oncosuppressor in preclinical models and selected human tumors. Evidence collected over the years suggests that PTX3 is a biomarker and potential therapeutic agent in humans, and pave the way to translation of this molecule into the clinic
Exploring the value sponsors co-create at a charity sport event: a multiple stakeholder perspective of sport value
No full textThe charity sport event experience is created by a wide array of stakeholders. This research explores value co-creation for charity sport event sponsors. Specifically, the purpose of the current research is to examine charity sport event sponsors’ and managers’ perceptions of how sponsors co-create value in the charity sport event context. Semi-structured interviews were conducted with charity sport event sponsors (n = 5) and charity sport event managers (n = 5). Within the interviews with sponsor representatives, one theme, sponsor contributions as symbolic contributions, and two categories: giving beyond financial contribution and internal awareness were uncovered. One theme, sponsors as event advocates, and two categories, cause amplification and employee participation, emerged from the interviews with event managers. The interviews also revealed similarities in the perceptions of sponsor managers and event managers in that sponsor employees are viewed as important advocates for the cause and partnership. Meanwhile, differences between the two groups emerged as event managers spoke explicitly about importance of financial contributions from the sponsors, while sponsorship managers highlighted how the sponsorship went beyond the monetary aspects. The findings can be integrated into event management strategy to create off-site event initiatives and to use digital storytelling facilitate engagement between the event and sponsor.Full Tex
The discovery of small-molecule inhibitors of keap1-nrf2 interaction with homogeneous fluorescence-based high throughput screening assays
No full textKeap1-Nrf2 interaction is a key protein-protein interaction involved in the activation of antioxidant response element which regulates the expression of cytoprotective enzymes in response to oxidative stress conditions. To identify direct inhibitors of Keap1-Nrf2 interaction, a series of fluorescently-labeled Nrf2 peptides were synthesized and evaluated as tracers in the development of a fluorescence polarization (FP) assay. The optimized tracer, FITC-9mer Nrf2 amide, was determined to have the highest binding affinity and dynamic range of all tracers evaluated. The FP assay has considerable tolerance towards DMSO and was capable of distinguishing the inhibitory Nrf2 peptides with a Z'-factor of 0.70 as determined under the FP assay conditions. Taken together, these results demonstrate that the FP assay is suitable for application in high-throughput screening (HTS). In addition, a series of novel lanthanide chelates were designed, synthesized, and evaluated for the development of a time-resolved fluorescence resonance energy transfer (TR-FRET) assay using an in situ labeling approach. The cyclam and EDTA-based tris-NTA were found to have the strongest affinity to the His6-tag of Keap1 Kelch domain with a Kd of 1.6 nM and 2.2 nM, respectively. Among the tris-NTA conjugates evaluated as donors of TR-FRET, the EDTA-tris-NTA Acp6-linker conjugate was found to have the highest TR-FRET signal. The in situ labeling technique was also evaluated for Eu(III) chelate and through biotin-streptavidin interaction, increasing the choice of fluorophores and extending the application of the assay to biotinylated biomolecules. Thus, the novel labeling reagent provides an excellent solution for facile development of TR-FRET assays in drug discovery. The FP assay was adapted for HTS of the NIH MLPCN library. Eight confirmed hits were obtained and one of the promising hits (LH602) was targeted for preliminary structure-activity relationship (SAR) studies. Among the synthesized compounds, 2,4,6-trimethylbenzenesulfonamide substituted analog 81 showed the highest affinity to Keap1 Kelch domain. However, LH602 was found to be unstable due to its naphthoquinone structure with a half-life of 6 hours in the assay buffer. Further SAR studies are needed to improve the binding affinity as well as stability of the compound in our effort to identify potent inhibitors of Keap1-Nrf2 interaction.Ph.D.Includes bibliographical referencesby Daigo Inoyam
Memorialized in Verse: Hideyoshi's Daigo Hanami of 1598
No full textAuthor Institution: University of Virgini
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