ATF3 Plays a Key Role in Kdo2-Lipid A-Induced TLR4-Dependent Gene Expression via NF-κB Activation

Background: Activating transcription factor 3 (ATF3) is a negative regulator of proinflammatory cytokine expression in macrophages, and ATF3 deficient mice are more susceptible to endotoxic shock. This study addresses the role of ATF3 in the Kdo 2-Lipid A-induced Toll-like receptor 4 (TLR4) signaling pathway in mouse embryonic fibroblasts (MEF). Kdo 2-Lipid A upregulates ATF3 expression in wild type MEF cells and induces both nuclear factor kappa B (NF-kB) and c-Jun N-terminal kinase (JNK) activation via the TLR4 signaling pathway, while neither of these pathways is activated in ATF3-/- MEF cells. Interestingly, in contrast to Kdo 2-Lipid A, the activation of both NF-kB and JNK by TNF-a was normal in ATF3-/- MEF cells. Methodology/Principal Findings: We found that several genes were dramatically upregulated in ATF3+/+ MEF cells in response to Kdo2-Lipid A treatment, while little difference was observed in the ATF3-/- MEF cells. However, we also found that the signal intensities of IkBf in ATF3-/- MEF cells were substantially higher than those in wild type MEF cells upon microarray analyses, and upregulated IkBf expression was detected in the cytosol fraction. Conclusions/Significance: Our findings indicate that ATF3 deficiency affects Kdo 2-Lipid A-induced TLR4 signaling pathways in MEF cells, that it may upregulate IkBf expression and that the high levels of IkBf expression in ATF3-/- cells disrupts Kdo2-Lipid A-mediated signaling pathways

Games of Incomplete Information and Myopic Equilibria

A new concept of an equilibrium in games is introduced that solves an open question posed by A. Neyman

Development of a glycoconjugate vaccine to prevent invasive Salmonella Typhimurium infections in sub-Saharan Africa

Invasive infections associated with non-typhoidal Salmonella (NTS) serovars Enteritidis (SE), Typhimurium (STm) and monophasic variant 1,4,[5],12:i:- are a major health problem in infants and young children in sub-Saharan Africa, and currently, there are no approved human NTS vaccines. NTS O-polysaccharides and flagellin proteins are protective antigens in animal models of invasive NTS infection. Conjugates of SE core and O-polysaccharide (COPS) chemically linked to SE flagellin have enhanced the anti-COPS immune response and protected mice against fatal challenge with a Malian SE blood isolate. We report herein the development of a STm glycoconjugate vaccine comprised of STm COPS conjugated to the homologous serovar phase 1 flagellin protein (FliC) with assessment of the role of COPS O-acetyls for functional immunity. Sun-type COPS conjugates linked through the polysaccharide reducing end to FliC were more immunogenic and protective in mice challenged with a Malian STm blood isolate than multipoint lattice conjugates (>95% vaccine efficacy [VE] versus 30-43% VE). Immunization with de-O-acetylated STm-COPS conjugated to CRM197 provided significant but reduced protection against STm challenge compared to mice immunized with native STm-COPS:CRM197 (63-74% VE versus 100% VE). Although OPS O-acetyls were highly immunogenic, post-vaccination sera that contained various O-acetyl epitope-specific antibody profiles displayed similar in vitro bactericidal activity when equivalent titers of anti-COPS IgG were assayed. In-silico molecular modeling further indicated that STm OPS forms a single dominant conformation, irrespective of O-acetylation, in which O-acetyls extend outward and are highly solvent exposed. These preclinical results establish important quality attributes for an STm vaccine that could be co-formulated with an SE-COPS:FliC glycoconjugate as a bivalent NTS vaccine for use in sub-Saharan Africa

Root canal filling removal during endodontic retreatment - a survey of Ghanaian dentists

Background : Endodontic treatment aims to thoroughly clean and shape the root canal system to rid it of any infected pulpal tissue or bacteria and to provide a three-dimensional hermetic seal to the root canal system to prevent re-infection. Despite the high rates of success of endodontic treatment, failures do occur, and these may be attributed to the persistence of bacteria in the root canal system, lack of a hermetic seal during obturation, inadequate condensation of gutta-percha, inadequate cleaning and shaping of the canal, coronal leakage or the presence of unidentified accessory canals.For successful endodontic retreatment to occur, all traces of the root filling material (gutta-percha and the sealant) must be removed from the canal walls to enable access to the apical third of the root canal system to be regained. Removal of gutta-percha can be carried out by thermal, laser, chemical, and mechanical techniques or a combination of the above.General Aim : To determine which instruments and solvents Ghanaian dentists use to remove gutta-percha during endodontic retreatment.Methodology : A cross-sectional study was done by giving out a structured questionnaire at a Continuous Professional Development (CPD) event held for dentists. Simple descriptive statistics were used together with Chi-square (χ2) and one-way Analysis of Variance (ANOVA) tests. The chosen level of significance was set at p < 0.05. Unanswered questions were treated as missing values.Results : A total of 64 dental practitioners were surveyed in this study. 32 out of 63(50.8%) respondents performed 2-4 root canal treatments (RCTs) per week, and 49 out of 62(79.0%) performed 0-1% of re-RCTs per week. 59 out of 62(95.2%) practitioners used hand files during root canal treatment. 44 out of 57(77.2 %) practitioners used hand files in combination with solvents, Gates Glidden burs, and barbed broaches during endodontic retreatment. Eucalyptol was the most used solvent during endodontic retreatment, accounting for 31 out of 39(79.5%) positive responses by practitioners.Conclusion : Most Ghanaian dentists use hand files (K-files-54.3%) with solvents (Eucalyptol-79.5%) in the removal of gutta-percha during endodontic retreatment

Comparative analysis of hatcheries contribution to poor development of day-old chicks based on biological and immunological performance

Background and Aim: The quality of day-old chicks is a cornerstone to successful poultry production. Chicks with a poor quality start slowly in the field and may have high feed intake, poor growth rate, and poor feed conversion ratio. The current study aimed to assess chick quality challenges encountered from day-old chicks hatched in most commercial hatcheries in Ghana. Materials and Methods: A total of 300 day-old chicks each were obtained from commercial hatcheries in Ghana and Europe. The chicks were labeled as locally hatched broiler day-old chicks (LBDOC) and foreign hatched broiler day-old chicks (FBDOC), respectively. Chicks were reared and monitored from day old to 21 days post-hatch. Sample of chicks (n=25) from each hatchery was euthanized weekly at 1, 7, 14, and 21 days and blood samples collected for analysis. The parameters measured included physical, hematological, immunological, histological, and bacteriological characteristics. All data were analyzed by SAS Proc GLM at p<0.05. Results: The live weight of chicks was higher in FBDOC compared to LBDOC on the 1st day. The chick length and shank length of FBDOC were longer than the LBDOC. The 7-day chick mortality was 6% in LBDOC as compared to 1.5% in FBDOC. The LBDOC also had a higher wet and dry residual yolk sac percentages as well as higher residual yolk sac fluid volume than the FBDOC. The rate of yolk sac disappearance of the FBDOC was higher than the LBDOC. More than half of the LBDOC had developed navel strings and leaky navel compared to FBDOC. The LBDOC recorded Escherichia coli, Proteus, Streptococcus spp., and Gram-negative bacteria in the residual yolk sac isolated through the 21 days while FBDOC recorded E. coli, Proteus, and Gram-negative bacteria. The intestinal villi count, lengths, width, and surface area were all not significantly different. The blood monocyte levels appeared higher in FBDOC than LBDOC, which give evidence of higher immunity in FBDOC than LBDOC. Conclusion: The results indicate a challenging situation in maintaining the quality of locally hatched broiler day-old-chicks compared to foreign hatched broiler-day-old-chicks. The study demonstrates that chick quality impact goes beyond the physical characteristics of chick weight and chick length, and the higher performance of FBDOC may be influenced by compliance with international hatchery standards and vaccination protocols