Mapping the interaction of B cell Leukemia 3 (BCL-3) and nuclear factor κB (NF-κB) p50 identifies a BCL-3-mimetic anti-inflammatory peptide

The NF-κB transcriptional response is tightly regulated by a number of processes including the phosphorylation, ubiquitination, and subsequent proteasomal degradation of NF-κB subunits. The IκB family protein BCL-3 stabilizes a NF-κB p50 homodimer·DNA complex through inhibition of p50 ubiquitination. This complex inhibits the binding of the transcriptionally active NF-κB subunits p65 and c-Rel on the promoters of NF-κB target genes and functions to suppress inflammatory gene expression. We have previously shown that the direct interaction between p50 and BCL-3 is required for BCL-3-mediated inhibition of pro-inflammatory gene expression. In this study we have used immobilized peptide array technology to define regions of BCl-3 that mediate interaction with p50 homodimers. Our data show that BCL-3 makes extensive contacts with p50 homodimers and in particular with ankyrin repeats (ANK) 1, 6, and 7, and the N-terminal region of Bcl-3. Using these data we have designed a BCL-3 mimetic peptide based on a region of the ANK1 of BCL-3 that interacts with p50 and shares low sequence similarity with other IκB proteins. When fused to a cargo carrying peptide sequence this BCL-3-derived peptide, but not a mutated peptide, inhibited Toll-like receptor-induced cytokine expression in vitro. The BCL-3 mimetic peptide was also effective in preventing inflammation in vivo in the carrageenan-induced paw edema mouse model. This study demonstrates that therapeutic strategies aimed at mimicking the functional activity of BCL-3 may be effective in the treatment of inflammatory disease

Expanding the understanding of majority-bias in children’s social learning

Prior experiments with children across seven different societies have indicated U-shaped age patterns in the likelihood of copying majority demonstrations. It is unclear which learning strategies underlie the observed responses that create these patterns. Here we broaden the understanding of children’s learning strategies by: (1) exploring social learning patterns among 6–13-year-olds (n = 270) from ethnolinguistically varied communities in Vanuatu; (2) comparing these data with those reported from other societies (n = 629), and (3) re-analysing our and previous data based on a theoretically plausible set of underlying strategies using Bayesian methods. We find higher rates of social learning in children from Vanuatu, a country with high linguistic and cultural diversity. Furthermore, our results provide statistical evidence for modest U-shaped age patterns for a more clearly delineated majority learning strategy across the current and previously investigated societies, suggesting that the developmental mechanisms structuring majority bias are cross-culturally highly recurrent and hence a fundamental feature of early human social learning

A Closer Look at Dietary Supplements: An Exercise in Experiential Learning

undergraduate poster presentatio

Comparison of two configurations of upflow anaerobic filters : specific methanogenic activity profiles

The aim of this work was to determine the distribution of microbial activity along the height of two configurations of anaerobic filters treating a synthetic dairy waste. A traditional configuration was compared with a staged system which had biogas removal from each of the three stages. The effect of increasing the substrate concentration from 3 to 12 g COD/l at constant hydraulic residence time (HRT) of 2 days was evaluated with respect to overall reactor performance, gas production and effluent volatile fatty acids profiles. The potential maximum specific methanogenic activity against acetate, H2/CO2 and an indirect substrate (propionate) was determined for sludge sampled from three different points in each reactor, under two operating conditions (influent COD of 3 and 9 g COD/l). The increase in influent concentration was shown to promote a stratification of the specific acetoclastic activity more pronounced in the staged reactor. Both the hydrogenophilic and acetoclastic activities were highest at the top of the filters, whereas the methanogenic activity against propionate was maximum in the middle section and was very similar for both reactor configurations. The results confirmed the reliability of the pressure transducer technique to study methanogenic activity of different trophic groups in consortia

Staged and non staged anaerobic filters : microbial selection, hydrodynamic aspects and performance

This work reports on the study of a staged and a non staged anaerobic filter treating a synthetic dairy waste under similar operating conditions. The effect of increasing the substrate concentration from 3 to 12 g COD/l at a constant hydraulic residence time (HRT) of 2 days was evaluated with respect to overall reactor performance, gas production and volatile fatty acids profiles along the height. The potential maximum specific methanogenic activity against acetate, H2/CO2, two indirect substrates (propionate and butyrate) and the lactose specific activity were determined for sludge sampled from three different points in each reactor, under two operating conditions (influent COD of 3 and 9 g COD/l). Although all microbial phases of anaerobic process were found throughout the reactors, it was possible to identify different specific sludges at different heights in both reactors. The pressure transducer technique applied was proven to be a reliable method to study methanogenic activity of different trophic groups in consortia. Performances of the two configurations were very similar under the operating conditions tested and the plug flow behaviour of the staged reactor was clearly reduced when the influent concentration increased from 3 to 9 g COD/l

Development of Nutrition Curriculum for Adults with I/DD: Part of a Mentoring Program to Improve Nutrition Knowledge and Self-Efficacy

poster presentation undergraduate - Gregory Lon

Interleukin-8 levels and activity in delayed-healing human thermal wounds

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72020/1/j.1524-475x.2000.00216.x.pd

Community-level education accelerates the cultural evolution of fertility decline.

Explaining why fertility declines as populations modernize is a profound theoretical challenge. It remains unclear whether the fundamental drivers are economic or cultural in nature. Cultural evolutionary theory suggests that community-level characteristics, for example average education, can alter how low-fertility preferences are transmitted and adopted. These assumptions have not been empirically tested. Here, we show that community-level education accelerates fertility decline in a way that is neither predicted by individual characteristics, nor by the level of economic modernization in a population. In 22 high-fertility communities in Poland, fertility converged on a smaller family size as average education in the community increased-indeed community-level education had a larger impact on fertility decline than did individual education. This convergence was not driven by educational levels being more homogeneous, but by less educated women having fewer children than expected, and more highly educated social networks, when living among more highly educated neighbours. The average level of education in a community may influence the social partners women interact with, both within and beyond their immediate social environments, altering the reproductive norms they are exposed to. Given a critical mass of highly educated women, less educated neighbours may adopt their reproductive behaviour, accelerating the pace of demographic transition. Individual characteristics alone cannot capture these dynamics and studies relying solely on them may systematically underestimate the importance of cultural transmission in driving fertility declines. Our results are inconsistent with a purely individualistic, rational-actor model of fertility decline and suggest that optimization of reproduction is partly driven by cultural dynamics beyond the individual

Quaternary structure independent folding of voltage-gated ion channel pore domain subunits

Every voltage-gated ion channel (VGIC) has a pore domain (PD) made from four subunits, each comprising an antiparallel transmembrane helix pair bridged by a loop. The extent to which PD subunit structure requires quaternary interactions is unclear. Here, we present crystal structures of a set of bacterial voltage-gated sodium channel (BacNaV) 'pore only' proteins that reveal a surprising collection of non-canonical quaternary arrangements in which the PD tertiary structure is maintained. This context-independent structural robustness, supported by molecular dynamics simulations, indicates that VGIC-PD tertiary structure is independent of quaternary interactions. This fold occurs throughout the VGIC superfamily and in diverse transmembrane and soluble proteins. Strikingly, characterization of PD subunit-binding Fabs indicates that non-canonical quaternary PD conformations can occur in full-length VGICs. Together, our data demonstrate that the VGIC-PD is an autonomously folded unit. This property has implications for VGIC biogenesis, understanding functional states, de novo channel design, and VGIC structural origins

Preparation and Antimicrobial Properties of Alginate and Serum Albumin/Glutaraldehyde Hydrogels Impregnated with Silver(I) Ions

peer-reviewedCalcium alginate (CaALG) hydrogel beads and two sets of composite beads, formed from a combination of calcium alginate/propylene glycol alginate/human serum albumin (CaALG/PGA/ HSA) and from calcium alginate with the quaternary ammonium salt, (3-(trimethoxysilyl)propyl)- octadecyldimethylammonium chloride (QA), (CaALG/QA), were prepared. Bovine serum albumin (BSA) was condensed with glutaraldehyde (GLA) to form a BSA/GLA hydrogel. The corresponding Ag+-containing gels of all of the above hydrogels were also formed, and slow leaching of the biocidal transition metal ion from the gels bestowed broad spectrum antimicrobial activity. In the absence of added Ag+, CaALG/QA was the only material to deliver marginal to moderate antibacterial and antifungal effects. The Ag+ impregnated hydrogel systems have the potential to maintain the antimicrobial properties of silver, minimising the risk of toxicity, and act as reservoirs to afford ongoing sterility.Irish Department of Agriculture Food and Marin