Peptide mapping of bacterial fimbrial epitopes interacting with pattern recognition receptors

The fimbriae of the oral pathogen Porphyromonas gingivalis induce Toll-like receptor 2 (TLR2)-dependent macrophage activation upon their recognition by CD14 and the beta(2) integrin CD11b/CD18. To map functional epitopes of fimbriae that interact with these pattern recognition receptors (PRRs), we examined 20 synthetic peptides covering the entire length of the 41-kDa fimbrillin subunit. Using direct or competitive inhibition assays for receptor binding or cell activation, the CD14 binding activity of fimbriae was localized to residues 69-90 and was essential for TLR2-dependent cytokine induction. The CD11b/CD18 binding activity of fimbriae was localized to two neighboring epitopes defined by residues 166-185 and 206-225. Unlike epitope 69-90 that constitutively bound CD14, the CD11b/CD18 binding activity of epitopes 166-185 and 206-225 was inducible by integrin activators. The CD11b/CD18 binding activity played a contributory role to TLR2-dependent induction of tumor necrosis factor-alpha by fimbriae but was involved in specific down-regulation of interleukin-12. Cell activation by a combination of fimbrillin peptides corresponding to the CD14 and CD11b/CD18 binding activities resulted in higher tumor necrosis factor-alpha responses than would be expected from a simply additive effect, attributable to CD14-dependent inside-out signaling leading to enhanced binding interactions with CD11b/CD18. These data suggest that P. gingivalis fimbriae display a modular structure that interacts through discrete epitopes and in a regulated mode with distinct PRRs, which in turn differentially modulate the state of cell activation. Elucidation of pathogen interactions with PRRs at the molecular level may glean insight into host defense mechanisms as well as into microbial strategies that subvert innate immunity.     

Alkaloids from Oriciopsis glaberrima Engl. (Rutaceae)

Two alkaloid derivatives, oriciacridone A and B, were isolated from the stem bark of Oriciopsis glaberrima (Rutaceae). The structures were elucidated by a detailed spectroscopic analysis. The extract exhibited in vitro significant antimicrobial activity against a range of micro-organisms.     

Comparative life cycle assessment and life cycle costing of lodging in the Himalaya

Purpose

The main aim of the study is to assess the environmental and economic impacts of the lodging sector located in the Himalayan region of Nepal, from a life cycle perspective. The assessment should support decision making in technology and material selection for minimal environmental and economic burden in future construction projects.

Methods

The study consists of the life cycle assessment and life cycle costing of lodging in three building types: traditional, semi-modern and modern. The life cycle stages under analysis include raw material acquisition, manufacturing, construction, use, maintenance and material replacement. The study includes a sensitivity analysis focusing on the lifespan of buildings, occupancy rate and discount and inflation rates. The functional unit was formulated as the ‘Lodging of one additional guest per night’, and the time horizon is 50 years of building lifespan. Both primary and secondary data were used in the life cycle inventory.

Results and discussion

The modern building has the highest global warming potential (kg CO_2-eq) as well as higher costs over 50 years of building lifespan. The results show that the use stage is responsible for the largest share of environmental impacts and costs, which are related to energy use for different household activities. The use of commercial materials in the modern building, which have to be transported mostly from the capital in the buildings, makes the higher GWP in the construction and replacement stages. Furthermore, a breakdown of the building components shows that the roof and wall of the building are the largest contributors to the production-related environmental impact.

Conclusions

The findings suggest that the main improvement opportunities in the lodging sector lie in the reduction of impacts on the use stage and in the choice of materials for wall and roof.

     

Alcohol Consumption Practices among Married Women of Reproductive Age in Nepal: A Population Based Household Survey

BackgroundAlcohol chemically known as ethanol, causes several health, economic and social consequences across the world. Literatures suggest potential harm of alcohol drinking by pregnant women especially to the fetus and the mother. Despite anumber of significant public health problems related to alcohol consumption, this area has been ignored in Nepal and information at the national level is limited. Thus this study aimed at finding the prevalence of alcohol consumption among married women of reproductive age.MethodsA nationally representative household survey was carried out from April to August 2013 by taking 16 districts across all 15 eco administrative regions. From the selected districts, 86 village development committees and 14 municipalities were selected as primary sampling units using probability proportionate to size, followed by random selection of 3 wards from each primary sampling unit. Finally, 30 households within each ward were selected using systematic random sampling, and one married women of reproductive age from each household. A total of 9000 married women of reproductive age were interviewed using a semi-structured questionnaire, on alcohol consumption practices including environmental factors and socio demographic characteristics and were included in the analysis.ResultsNational prevalence of alcohol consumption ever among married women of reproductive age was 24.7% (95% CI:21.7–28.0), last 12 months 17.9% (95% CI:15.3–20.7) and last 30 days (current drinking) 11.8% (95% CI:9.8–14.1). There was substantial variation among the districts ranging from 2% to 60%. Multivariable analysis suggests women with no education or within formal education, dalit and janajatis ethnicity, whose husbands drink alcohol, who brew alcohol at home and women from mountains were significantly at higher risk of consuming alcohol. Among the women who drank alcohol in last 12 months, a substantial proportion of them drank home brewed alcoholic beverages (95.9%, 95% CI:94.3–97.4).ConclusionAlcohol consumption was common practice among married women of reproductive age in Nepal with variation among the subgroups of population. Thus, further investigation and behavior change communication interventions to reduce alcohol consumption especially among the women with higher risk of drinking is essential.     

Biomechanical Energy‐Driven Hybridized Generator as a Universal Portable Power Source for Smart/Wearable Electronics

The fast growth of smart electronics requires novel solutions to power them sustainably. Portable power sources capable of harvesting biomechanical energy are a promising modern approach to reduce battery dependency. Herein, a novel elastic impact‐based nonresonant hybridized generator (EINR‐HG) is reported to effectively harvest biomechanical energy from diverse human activities outdoors. Through the rational integration of a nonlinear electromagnetic generator with two contact‐mode triboelectric nanogenerators, the proposed EINR‐HG generates hybrid electrical output simultaneously under the same mechanical excitations. By introducing a flux‐concentrator with a nanowire‐nanofiber surface modification, significant improvement in the energy harvesting efficiency of the EINR‐HG is achieved. After optimizing using simulations and vibration tests, the as‐fabricated EINR‐HG delivers an outstanding normalized power density of 3.13 mW cm^?3 g^?2 across a matching resistance of 1.5 kΩ at 6 Hz under 1 g acceleration. Under human motion testing, the EINR‐HG generates an optimal output power of 131.4 mW with horizontal handshaking. With a customized power management circuit, the EINR‐HG serves as a universal power source that successfully drives commercial smart electronics, including smart bands and smartphones. This work shows the massive potential of biomechanical energy‐driven hybridized generators for powering personal electronics and portable healthcare monitoring devices.     

The Microbiological and Clinical Characteristics of Invasive Salmonella in Gallbladders from Cholecystectomy Patients in Kathmandu,Nepal

Gallbladder carriage of invasive Salmonella is considered fundamental in sustaining typhoid fever transmission. Bile and tissue was obtained from 1,377 individuals undergoing cholecystectomy in Kathmandu to investigate the prevalence, characteristics and relevance of invasive Salmonella in the gallbladder in an endemic area. Twenty percent of bile samples contained a Gram-negative organism, with Salmonella Typhi and Salmonella Paratyphi A isolated from 24 and 22 individuals, respectively. Gallbladders that contained Salmonella were more likely to show evidence of acute inflammation with extensive neutrophil infiltrate than those without Salmonella, corresponding with higher neutrophil and lower lymphocyte counts in the blood of Salmonella positive individuals. Antimicrobial resistance in the invasive Salmonella isolates was limited, indicating that gallbladder colonization is unlikely to be driven by antimicrobial resistance. The overall role of invasive Salmonella carriage in the gallbladder is not understood; here we show that 3.5% of individuals undergoing cholecystectomy in this setting have a high concentration of antimicrobial sensitive, invasive Salmonella in their bile. We predict that such individuals will become increasingly important if current transmission mechanisms are disturbed; prospectively identifying these individuals is, therefore, paramount for rapid local and regional elimination.     

The contributions of nitrogen-fixing crop legumes to the productivity of agricultural systems

Data collated from around the world indicate that, for every tonne of shoot dry matter produced by crop legumes, the symbiotic relationship with rhizobia is responsible for fixing, on average on a whole plant basis (shoots and nodulated roots), the equivalent of 30–40 kg of nitrogen (N). Consequently, factors that directly influence legume growth (e.g. water and nutrient availability, disease incidence and pests) tend to be the main determinants of the amounts of N₂ fixed. However, practices that either limit the presence of effective rhizobia in the soil (no inoculation, poor inoculant quality), increase soil concentrations of nitrate (excessive tillage, extended fallows, fertilizer N), or enhance competition for soil mineral N (intercropping legumes with cereals) can also be critical. Much of the N₂ fixed by the legume is usually removed at harvest in high-protein seed so that the net residual contributions of fixed N to agricultural soils after the harvest of legumegrain may be relatively small.Nonetheless, the inclusion of legumes in a cropping sequence generally improves the productivity of following crops. Whilesome of these rotational effects may be associated with improvements in availability of N in soils, factors unrelated to N also play an important role. Recent results suggest that one such non-N benefit may be due to the impact on soil biology of hydrogenemitted from nodules as a by-product of N₂, fixation.     

Differential interactions of fimbriae and lipopolysaccharide from Porphyromonas gingivalis with the Toll-like receptor 2-centred pattern recognition apparatus

The lipopolysaccharide (LPS) and fimbriae of Porphyromonas gingivalis play important roles in periodontal inflammation and pathogenesis. We investigated fimbriae and LPS from several P. gingivalis strains in terms of relative dependence on Toll-like receptor (TLR) signalling partners or accessory pattern-recognition molecules mediating ligand transfer to TLRs, and determined induced assembly of receptor complexes in lipid rafts. Fimbriae could utilize TLR1 or TLR6 for cooperative TLR2-dependent activation of transfected cell lines, in contrast to LPS and a mutant version of fimbriae which displayed preference for TLR1. Whether used to activate human cell lines or mouse macrophages, fimbriae exhibited strong dependence on membrane-expressed CD14 (mCD14), which could not be substituted for by soluble CD14 (sCD14). In contrast, sCD14 efficiently substituted for mCD14 in LPS-induced cellular activation. LPS-binding protein was more important for LPS- than for fimbria-induced cell activation, whereas the converse was true for CD11b/CD18. Cell activation by LPS or fimbriae required lipid raft function and formation of heterotypic receptor complexes (TLR1-2/CD14/CD11b/CD18), although wild-type fimbriae additionally recruited TLR6. In summary, TLR2 activation by P. gingivalis LPS or fimbriae involves differential dependence on accessory signalling or ligand-binding receptors, which may differentially influence innate immune responses.     

Using sensor web protocols for environmental data acquisition and management

Standard interfaces for data and information access facilitate data management and usability by minimizing the effort required to acquire, catalog and integrate data from a variety of sources. The authors have prototyped several data management and analysis applications using Sensor Web Enablement Services, a suite of service protocols being developed by the Open Geospatial Consortium specifically for handling sensor data in near-real time. This paper provides a brief overview of some of the service protocols and describes how they are used in various sensor web projects involving near-real-time management of sensor data.