scholarly journals The Role of RSV Infection in Asthma Initiation and Progression: Findings in a Mouse Model

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Junyan Han ◽  
Katsuyuki Takeda ◽  
Erwin W. Gelfand
Keyword(s):  
Experimental Models ◽  
Valuable Insight ◽  
Recurrent Wheezing ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Underlying Mechanisms ◽  
Infancy And Early Childhood ◽  
Severe Pulmonary Disease ◽  
Insight Into

Respiratory syncytial virus (RSV) is a common cause of severe lower respiratory tract diseases (bronchiolitis and pneumonia) during infancy and early childhood. There is increasing evidence which indicates that severe pulmonary disease caused by RSV infection in infancy is associated with recurrent wheezing and development of asthma later in childhood. However, the underlying mechanisms linking RSV infection to persistent airway hyperresponsiveness and dysfunction are not fully defined. To study these processes in ways which are not available in humans, animal models have been established and have provided valuable insight into the pathophysiology of RSV-induced disease. In this paper, we discuss experimental models of RSV infection in mice and highlight a new investigative approach in which mice are initially infected as neonates and then reinfected later in life. The findings shed light on the mechanisms underlying the association between early severe RSV infection and development of asthma later in childhood.

RESPIRATORY SYNCYTIAL VIRUS LUNG INFECTION IN INFANTS: IMMUNOREGULATORY ROLE OF INFECTED ALVEOLAR MACROPHAGES

PEDIATRICS ◽  
1995 ◽  
Vol 96 (2) ◽  
pp. 391-391
Author(s):  
Leon S. Greos
Keyword(s):  
Immune Response ◽  
Respiratory Syncytial Virus ◽  
Lung Injury ◽  
Alveolar Macrophages ◽  
Lung Infection ◽  
Local Immune Response ◽  
Rsv Infection ◽  
Syncytial Virus

Alveolar macrophages are infected by RSV in vivo and coexpress potent immunomodulatory molecules that potentially regulate local immune response or lung injury caused by RSV infection.

The Role of Digital Libraries in Supporting Open Distance E-Learning

2021 ◽  
pp. 245-257
Author(s):  
Vusi W. Tsabedze
Keyword(s):  
Digital Library ◽  
Digital Libraries ◽  
Valuable Insight ◽  
Electronic Resources ◽  
E Learning ◽  
Teaching Learning ◽  
Insight Into

This chapter aims to discuss the potential of digital libraries to offer unparalleled resources for supporting open distance e-learning (ODeL). This chapter addresses and discusses such features as what is meant by ODeL and how it can be supported by the library and the functionality of the digital library, and how ODeL resources are included and organised in the digital library environment. The chapter explores the advantages of digital libraries for ODeL and the types of learning that can be supported by digital libraries. There is surely an interest in the usage of electronic resources for teaching, learning, and research, but this appears to be matched by a lack of awareness of how best to assimilate these resources into ODeL. The chapter provides valuable insight into the role and influence of digital libraries and e-resources on ODeL.

The Cognitive Component of Elite High Jumpers’ Preperformance Routines

2020 ◽  
Vol 34 (2) ◽  
pp. 99-110
Author(s):  
Thomas Gretton ◽  
Lindsey Blom ◽  
Dorice Hankemeier ◽  
Lawrence Judge
Keyword(s):  
Thematic Analysis ◽  
Critical Role ◽  
Valuable Insight ◽  
Psychological Skills ◽  
Cognitive Content ◽  
Successful Performance ◽  
Cognitive Component ◽  
Inductive Thematic Analysis ◽  
Insight Into

Preperformance routines are microlevel performance processes utilized by athletes to facilitate the attainment of an optimal state and enhance the chance for successful performance. Despite continued examination of these routines, only a small proportion of research has been directed toward the cognitive component of these routines. This study explored the cognitive component of elite high jumpers’ preperformance routines, and specifically the consistency of the cognitive content (i.e., psychological skills and strategies). Data were acquired over an 8-week high-jump season and subjected to inductive thematic analysis. Results revealed the consistent implementation of the cognitive content (e.g., visualization) but an inconsistent design of this content (i.e., the content of the visualization). Furthermore, results underline the critical role of high-jump coaches and an athlete’s need to be adaptable and competent in utilizing various types of preperformance routine. This study offers valuable insight into the complexities and inconsistencies of the cognitive component of high jumpers’ preperformance routines.

scholarly journals Central Role of the NF-κB Pathway in theScgb1a1-Expressing Epithelium in Mediating Respiratory Syncytial Virus-Induced Airway Inflammation

2018 ◽  
Vol 92 (11) ◽  
Author(s):  
Bing Tian ◽  
Jun Yang ◽  
Yingxin Zhao ◽  
Teodora Ivanciuc ◽  
Hong Sun ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Lower Respiratory Tract ◽  
Pol Ii ◽  
Neutrophilic Inflammation ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Epithelial Cell Population

ABSTRACTLower respiratory tract infection with respiratory syncytial virus (RSV) produces profound inflammation. Despite an understanding of the role of adaptive immunity in RSV infection, the identity of the major sentinel cells initially triggering inflammation is controversial. Here we evaluate the role of nonciliated secretoglobin (Scgb1a1)-expressing bronchiolar epithelial cells in RSV infection. Mice expressing a tamoxifen (TMX)-inducible Cre recombinase-estrogen receptor fusion protein (CreERTM) knocked into theScgb1a1locus were crossed with mice that harbor aRelAconditional allele (RelAfl), with loxP sites flanking exons 5 to 8 of the Rel homology domain. TheScgb1a1CreERTM/+× RelAfl/flmouse is aRelAconditional knockout (RelACKO) of a nonciliated epithelial cell population enriched in the small bronchioles. TMX-treated RelACKOmice have reduced pulmonary neutrophilic infiltration and impaired expression and secretion of NF-κB-dependent cytokines in response to RSV. In addition, RelACKOmice had reduced expression levels of interferon (IFN) regulatory factor 1/7 (IRF1/7) and retinoic acid-inducible gene I (RIG-I), components of the mucosal IFN positive-feedback loop. We demonstrate that RSV replication induces RelA to complex with bromodomain-containing protein 4 (BRD4), a cofactor required for RNA polymerase II (Pol II) phosphorylation, activating the atypical histone acetyltransferase (HAT) activity of BRD4 required for phospho-Ser2 Pol II formation, histone H3K122 acetylation, and cytokine secretionin vitroandin vivo. TMX-treated RelACKOmice have less weight loss and reduced airway obstruction/hyperreactivity yet similar levels of IFN-γ production despite higher levels of virus production. These data indicate that the nonciliatedScgb1a1-expressing epithelium is a major innate sensor for restricting RSV infection by mediating neutrophilic inflammation and chemokine and mucosal IFN production via the RelA-BRD4 pathway.IMPORTANCERSV infection is the most common cause of infant hospitalizations in the United States, resulting in 2.1 million children annually requiring medical attention. RSV primarily infects nasal epithelial cells, spreading distally to produce severe lower respiratory tract infections. Our study examines the role of a nonciliated respiratory epithelial cell population in RSV infection. We genetically engineered a mouse that can be selectively depleted of the NF-κB/RelA transcription factor in this subset of epithelial cells. These mice show an impaired activation of the bromodomain-containing protein 4 (BRD4) coactivator, resulting in reduced cytokine expression and neutrophilic inflammation. During the course of RSV infection, epithelial RelA-depleted mice have reduced disease scores and airway hyperreactivity yet increased levels of virus replication. We conclude that RelA-BRD4 signaling in nonciliated bronchiolar epithelial cells mediates neutrophilic airway inflammation and disease severity. This complex is an attractive target to reduce the severity of infection.

The Role of Notch-Notch Ligand Signaling in Primary and Secondary Respiratory Syncytial Virus (RSV) Infection

2011 ◽  
Vol 127 (2) ◽  
pp. AB147-AB147
Author(s):  
J. Han ◽  
M. Okamoto ◽  
K. Takeda ◽  
K. Yasutomo ◽  
E.W. Gelfand
Keyword(s):  
Respiratory Syncytial Virus ◽  
Notch Ligand ◽  
Rsv Infection ◽  
Syncytial Virus

Impact of Boron and Gallium on Defects Production in Silicon

2000 ◽  
Vol 650 ◽  
Author(s):  
Aurangzeb Khan ◽  
Nethaji Dharmarasu ◽  
Masafumi Yamaguchi ◽  
Kenji Araki ◽  
Tuong K. Vu ◽  
...  
Keyword(s):  
Recombination Center ◽  
Valuable Insight ◽  
Electron Level ◽  
Boron Doped ◽  
Hole Level ◽  
Radiation Induced ◽  
Induced Defects ◽  
The Impact ◽  
Insight Into

ABSTRACTWe report the results of comparison of radiation-induced defects (1 MeV electrons) in n+-p-p+ Si diodes doped with gallium or boron ranging in concentration from 8 × 1014 to 5 × 1016 cm-3, together with the impact of oxygen on radiation –induced defects. Present results provide evidence for new defects states in addition to those previously reported in gallium- and boron-doped Si. The combined boron and gallium data provide enough information to gain valuable insight into the role of the dopants on radiation-induced defects in Si. The interesting new future of our results is that the gallium appears to strongly suppress the radiation induced defect, especially hole level EV+0.36 eV, which is thought to act as a recombination center. Similarly the dominant electron level at EC-0.18 eV in B-doped Si (which act as a donor) has not been observed in Ga-doped CZ-grown Si.

scholarly journals The Role of Toll-like receptor 4 in respiratory syncytial virus replication, interferon lambda 1 induction, and chemokine responses

2018 ◽  
Author(s):  
Lindsay Broadbent ◽  
Jonathon D. Coey ◽  
Michael D. Shields ◽  
Ultan F. Power
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
P38 Mapk ◽  
Inflammatory Cytokines ◽  
Virus Replication ◽  
Growth Kinetics ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Pro Inflammatory Cytokines

AbstractRespiratory syncytial virus (RSV) infection is the leading cause of severe lower respiratory tract infections (LRTI) in infants worldwide. The immune responses to RSV infection are implicated in RSV pathogenesis but RSV immunopathogenesis in humans remains poorly understood. We previously demonstrated that IFN-λ1 is the principle interferon induced following RSV infection of infants and well-differentiated primary pediatric bronchial epithelial cells (WD-PBECs). Interestingly, RSV F interacts with the TLR4/CD14/MD2 complex to initiate secretion of pro-inflammatory cytokines, while TLR4 stimulation with house dust mite induces IFN-λ1 production. However, the role of TLR4 in RSV infection and concomitant IFN-λ1 induction remains unclear. Using our RSV/WD-PBEC infection model, we found that CLI-095 inhibition of TLR4 resulted in significantly reduced viral growth kinetics, and secretion of IFN-λ1 and pro-inflammatory chemokines. To elucidate specific TLR4 signalling intermediates implicated in virus replication and innate immune responses we selected 4 inhibitors, including LY294002, U0126, SB203580 and JSH-23. SB203580, a p38 MAPK inhibitor, reduced both viral growth kinetics and IFN-λ1 secretion, while JSH-23, an NF-κB inhibitor, reduced IFN-λ1 secretion without affecting virus growth kinetics. Our data indicate that TLR4 plays a role in RSV entry and/or replication and IFN-λ1 induction following RSV infection is mediated, in part, by TLR4 signalling through NF- κB and/or p38 MAPK. Therefore, targeting TLR4 or downstream effector proteins could present novel treatment strategies against RSV.ImportanceThe role of TLR4 in RSV infection and IFN-λ1 induction is controversial. Using our WD-PBEC model, which replicates many hallmarks of RSV infection in vivo, we demonstrated that the TLR4 pathway is involved in both RSV infection and/or replication and the concomitant induction of IFN-λ1 and other pro-inflammatory cytokines. Increasing our understanding of the role of TLR4 in RSV immunopathogenesis may lead to the development of novel RSV therapeutics.

scholarly journals The Role of HDAC6 in Autophagy and NLRP3 Inflammasome

2021 ◽  
Vol 12 ◽  
Author(s):  
Panpan Chang ◽  
Hao Li ◽  
Hui Hu ◽  
Yongqing Li ◽  
Tianbing Wang
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammatory Diseases ◽  
Critical Role ◽  
Histone Deacetylase 6 ◽  
Physiological Processes ◽  
Class Iib ◽  
Underlying Mechanisms ◽  
Nlrp3 Inflammasomes ◽  
Insight Into

Autophagy fights against harmful stimuli and degrades cytosolic macromolecules, organelles, and intracellular pathogens. Autophagy dysfunction is associated with many diseases, including infectious and inflammatory diseases. Recent studies have identified the critical role of the NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasomes activation in the innate immune system, which mediates the secretion of proinflammatory cytokines IL-1β/IL-18 and cleaves Gasdermin D to induce pyroptosis in response to pathogenic and sterile stimuli. Accumulating evidence has highlighted the crosstalk between autophagy and NLRP3 inflammasome in multifaceted ways to influence host defense and inflammation. However, the underlying mechanisms require further clarification. Histone deacetylase 6 (HDAC6) is a class IIb deacetylase among the 18 mammalian HDACs, which mainly localizes in the cytoplasm. It is involved in two functional deacetylase domains and a ubiquitin-binding zinc finger domain (ZnF-BUZ). Due to its unique structure, HDAC6 regulates various physiological processes, including autophagy and NLRP3 inflammasome, and may play a role in the crosstalk between them. In this review, we provide insight into the mechanisms by which HDAC6 regulates autophagy and NLRP3 inflammasome and we explored the possibility and challenges of HDAC6 in the crosstalk between autophagy and NLRP3 inflammasome. Finally, we discuss HDAC6 inhibitors as a potential therapeutic approach targeting either autophagy or NLRP3 inflammasome as an anti-inflammatory strategy, although further clarification is required regarding their crosstalk.

scholarly journals Role of the Ubiquitin System in Chronic Pain

2021 ◽  
Vol 14 ◽  
Author(s):  
Jiurong Cheng ◽  
Yingdong Deng ◽  
Jun Zhou
Keyword(s):  
Chronic Pain ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Public Health Issue ◽  
Deubiquitinating Enzyme ◽  
Ubiquitin System ◽  
Significant Public Health ◽  
Underlying Mechanisms ◽  
Insight Into

As a significant public health issue, chronic pain, mainly neuropathic pain (NP) and inflammatory pain, has a severe impact. The underlying mechanisms of chronic pain are enigmatic at present. The roles of ubiquitin have been demonstrated in various physiological and pathological conditions and underscore its potential as therapeutic targets. The dysfunction of the component of the ubiquitin system that occurs during chronic pain is rapidly being discovered. These results provide insight into potential molecular mechanisms of chronic pain. Chronic pain is regulated by ubiquitination, SUMOylation, ubiquitin ligase, and deubiquitinating enzyme (DUB), etc. Insight into the mechanism of the ubiquitin system regulating chronic pain might contribute to relevant therapeutic targets and the development of novel analgesics.

scholarly journals Histone-Like Nucleoid Structuring Protein Modulates the Fitness of tet(X4)-Bearing IncX1 Plasmids in Gram-Negative Bacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenhui Cai ◽  
Feifei Tang ◽  
Lijie Jiang ◽  
Ruichao Li ◽  
Zhiqiang Wang ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Antibiotic Resistance Genes ◽  
Inhibitory Effect ◽  
Fitness Cost ◽  
Relative Fitness ◽  
Gram Negative Bacteria ◽  
Underlying Mechanisms ◽  
Biological Environment ◽  
Insight Into

The emergence of plasmid-mediated tigecycline resistance gene tet(X4) poses a challenging threat to public health. Based on the analysis of tet(X4)-positive plasmids in the NCBI database, we found that the IncX1-type plasmid is one of the most common vectors for spreading tet(X4) gene, but the mechanisms by which these plasmids adapt to host bacteria and maintain the persistence of antibiotic resistance genes (ARGs) remain unclear. Herein, we investigated the underlying mechanisms of how host bacteria modulate the fitness cost of IncX1 plasmids carrying tet(X4) gene. Interestingly, we found that the tet(X4)-bearing IncX1 plasmids encoding H-NS protein imposed low or no fitness cost in Escherichia coli and Klebsiella pneumoniae; instead, they partially promoted the virulence and biofilm formation in host bacteria. Regression analysis revealed that the expression of hns gene in plasmids was positively linked to the relative fitness of host bacteria. Furthermore, when pCE2::hns was introduced, the fitness of tet(X4)-positive IncX1 plasmid pRF55-1 without hns gene was significantly improved, indicating that hns mediates the improvement of fitness. Finally, we showed that the expression of hns gene is negatively correlated with the expression of tet(X4) gene, suggesting that the regulatory effect of H-NS on adaptability may be attributed to its inhibitory effect on the expression of ARGs. Together, our findings suggest the important role of plasmid-encoded H-NS protein in modulating the fitness of tet(X4)-bearing IncX1 plasmids, which shed new insight into the dissemination of tet(X4) gene in a biological environment.

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