HAGE,a cancer/testis antigen with potential for melanoma immunotherapy: identification of several MHC class I/II HAGE-derived immunogenic peptides

There remains a need to identify novel epitopes of potential tumour target antigens for use in immunotherapy of cancer. Here, several melanoma tissues and cell lines but not normal tissues were found to overexpress the cancer-testis antigen HAGE at the mRNA and protein level. We identified a HAGE-derived 15-mer peptide containing a shorter predicted MHC class I-binding sequence within a class II-binding sequence. However, only the longer peptide was found to be both endogenously processed and immunogenic for T cells in transgenic mice in vivo, as well as for human T cells in vitro. A different class I-binding peptide, not contained within a longer class II sequence, was subsequently found to be both immunogenic and endogenously processed in transgenic mice, as was a second class II epitope. These novel HAGE-derived epitopes may contribute to the range of immunotherapeutic targets for use in cancer vaccination programs.     

Cathepsin S controls MHC class II-mediated antigen presentation by epithelial cells in vivo

Epithelial cells at environmental interfaces provide protection from potentially harmful agents, including pathogens. In addition to serving as a physical barrier and producing soluble mediators of immunity, such as cytokines or antimicrobial peptides, these cells are thought to function as nonprofessional APCs. In this regard, intestinal epithelial cells are particularly prominent because they express MHC class II molecules at the site of massive antigenic exposure. However, unlike bone marrow-derived professional APC, such as dendritic cells or B cells, little is known about the mechanisms of MHC class II presentation by the nonprofessional APC in vivo. The former use the lysosomal cysteine protease cathepsin S (Cat S), whereas thymic cortical epithelial cells use cathepsin L (Cat L) for invariant chain degradation and MHC class II maturation. Unexpectedly, we found that murine Cat S plays a critical role in invariant chain degradation in intestinal epithelial cells. Furthermore, we report that nonprofessional APC present a class II-bound endogenous peptide to naive CD4 T cells in vivo in a Cat S-dependent fashion. These results suggest that in vivo, both professional and nonprofessional MHC class II-expressing APC use Cat S, but not Cat L, for MHC class II-mediated Ag presentation.     

Association between obesity and prescribed medication use in England

We investigate the association between obesity and use of prescribed medications in England. Data were taken from fourteen rounds of the Health Survey for England (1999–2012), which has measures of current prescribed medication use based on therapeutic classifications in the British National Formulary, and nurse-measured height and weight. We find that obesity has a statistically significant and positive association with use of a range of medicines for managing diseases associated with obesity. The mean probability of using any type of medication is 0.40 in those of normal weight, 0.44 in the overweight, 0.52 in obesity class I and 0.60 in obesity class II/III. Significant positive associations were found between obesity and the use of medication for diseases of the cardiovascular system, gastrointestinal system, respiratory system, and central nervous system, as well as for infections, endocrine system disorders, gynaecological/urinary disorders and musculoskeletal and joint disorders. Use of anti-obesity medication is low, even among those with class II/III obesity.     

The effectiveness of evidence summaries on health policymakers and health system managers use of evidence from systematic reviews: a systematic review

Background

Systematic reviews are important for decision makers. They offer many potential benefits but are often written in technical language, are too long, and do not contain contextual details which make them hard to use for decision-making. There are many organizations that develop and disseminate derivative products, such as evidence summaries, from systematic reviews for different populations or subsets of decision makers. This systematic review aimed to (1) assess the effectiveness of evidence summaries on policymakers’ use of the evidence and (2) identify the most effective summary components for increasing policymakers’ use of the evidence. We present an overview of the available evidence on systematic review derivative products.

Methods

We included studies of policymakers at all levels as well as health system managers. We included studies examining any type of “evidence summary,” “policy brief,” or other products derived from systematic reviews that presented evidence in a summarized form. The primary outcomes were the (1) use of systematic review summaries in decision-making (e.g., self-reported use of the evidence in policymaking and decision-making) and (2) policymakers’ understanding, knowledge, and/or beliefs (e.g., changes in knowledge scores about the topic included in the summary). We also assessed perceived relevance, credibility, usefulness, understandability, and desirability (e.g., format) of the summaries.

Results

Our database search combined with our gray literature search yielded 10,113 references after removal of duplicates. From these, 54 were reviewed in full text, and we included six studies (reported in seven papers) as well as protocols from two ongoing studies. Two studies assessed the use of evidence summaries in decision-making and found little to no difference in effect. There was also little to no difference in effect for knowledge, understanding or beliefs (four studies), and perceived usefulness or usability (three studies). Summary of findings tables and graded entry summaries were perceived as slightly easier to understand compared to complete systematic reviews. Two studies assessed formatting changes and found that for summary of findings tables, certain elements, such as reporting study event rates and absolute differences, were preferred as well as avoiding the use of footnotes.

Conclusions

Evidence summaries are likely easier to understand than complete systematic reviews. However, their ability to increase the use of systematic review evidence in policymaking is unclear.

Trial registration

The protocol was published in the journal Systematic Reviews (2015;4:122)

     

Why they eat,what they eat: patterns of wild edible plants consumption in a tribal area of Western Himalaya

Background

From time immemorial, wild plants have been used for edible purposes. They still continue to be a major source of nutrition for tribal people. However, unfortunately, their use is now declining. This has implications in food security, narrowing genetic base, and future leads. The present study was, therefore, carried out in Chhota Bhangal region of Western Himalaya to analyze uses of wild edible plants (WEP) and the motivations behind their use or abandonment.

Methods

Field surveys were conducted to the study area from January 2016 to March 2017. Household surveys, group discussions, free listing, and structured questionnaires were used to elicit information on WEP. WEP use was categorized into six categories (vegetables, fruits, chutney, flavoring food, raw food, and local brew). Trends of use (continuing, decreasing, increasing, and not used) and motivations (environmental, economic, sociocultural, agriculture and land use practices, and human-wildlife conflict) behind their use were analyzed.

Results

Fifty plant species were used by the local people for edible purposes under six WEP categories. Mean and median of WEP used per respondent was 22.3 and 21, respectively. Highest number of these were used as vegetable (mean 8.9) while lowest were used as brew (mean 0.4). Out of the 50 WEP used, 20 were prioritized for motivation analyses. Though plant use is still maintained in the area, changes are evident. Almost 50% of the respondents revealed that they still continue the use of WEP while 36% reported trends of declining use as compared to 5–10 years back. Close to 10% respondents have stopped consuming WEP now and ~?3% reported an increase in the use of WEP. Among the WEP categories, use of chutney showed an increasing trend. Sociocultural motivations were found to play a prime role, both, in limiting and promoting WEP use. Taste and aroma were the major sociocultural reasons behind using WEP while modernization and changing lifestyle were the main reasons behind declining use of WEP.

Conclusions

The study concludes that though use of WEP is still maintained in the area, changes in consumption trends are evident. Sociocultural motivations guided use of WEP in the area.

     

New <Emphasis Type="Italic">Bacillus subtilis</Emphasis> Strains as Promising Probiotics

The properties of new B. subtilis strains GM2 and GM5, isolated from potato rhizosphere and possessing high antimicrobial activity, were studied. The potential of the strains for their use as probiotics was characterized. The strains were resistant to bile and to a wide range of the ambient pH. B. subtilis strains GM2 and GM5 possessed proteolytic and phytate-hydrolyzing activity and proved to be safe for model animals. The strains were characterized by antagonistic properties against phytopathogenic micromycetes, as well as against pathogenic and opportunistic enterobacteria. B. subtilis GM2 and GM5 were concluded to be promising strains for use as probiotics.     

Social class as a risk factor for infant mortality in an Australian population

Studies in other countries have identified social class as a risk factor for infant mortality. In Australia there is no systematic collection of population data by social class, partly due to the absence of a recognized measure. The use of occupational prestige as an indicator of social class is discussed and Australian prestige scales reviewed. In a population based study, logistic regression analysis of infant mortality in an Australian (NSW) population shows the effects of social class on infant mortality which remain when maternal age, marital status and parity are controlled.     

Lambda Red-mediated recombinogenic engineering of enterohemorrhagic and enteropathogenic <Emphasis Type="Italic">E. coli</Emphasis>

Background

The λ Red recombineering technology has been used extensively in Escherichia coli and Salmonella typhimurium for easy PCR-mediated generation of deletion mutants, but less so in pathogenic species of E. coli such as EHEC and EPEC. Our early experiments with the use of λ Red in EHEC and EPEC have led to sporadic results, leading to the present study to identify factors that might improve the efficiency of Red recombineering in these pathogenic strains of E. coli.

Results

In this report, we have identified conditions that optimize the use of λ Red for recombineering in EHEC and EPEC. Using plasmids that contain a P_tac-red-gam operon and a temperature-sensitive origin of replication, we have generated multiple mutations (both marked and unmarked) in known virulence genes. In addition, we have easily deleted five O157-specific islands (O-islands) of EHEC suspected of containing virulence factors. We have examined the use of both PCR-generated substrates (40 bp of flanking homology) and plasmid-derived substrates (~1 kb of flanking homology); both work well and each have their own advantages. The establishment of the hyper-rec phenotype requires only a 20 minute IPTG induction period of red and gam. This recombinogenic window is important as constitutive expression of red and gam induces a 10-fold increase in spontaneous resistance to rifampicin. Other factors such as the orientation of the drug marker in recombination substrates and heat shock effects also play roles in the success of Red-mediated recombination in EHEC and EPEC.

Conclusions

The λ Red recombineering technology has been optimized for use in pathogenic species of E. coli, namely EHEC and EPEC. As demonstration of this technology, five O-islands of EHEC were easily and precisely deleted from the chromosome by electroporation with PCR-generated substrates containing drug markers flanked with 40 bp of target DNA. These results should encourage the use of λ Red recombineering in these and other strains of pathogenic bacteria for faster identification of virulence factors and the speedy generation of bacterial mutants for vaccine development.

     

Use of cultivated plants and non-plant remedies for human and animal home-medication in Liubań district,Belarus

Background

To use any domestic remedy, specific knowledge and skills are required. Simple logic dictates that the use of wild plants in the context of limited interaction with nature requires prior identification, while in the case of non-plant remedies and cultivated plants this step can be omitted. This paper aims to document the current and past uses of non-plant remedies and cultivated plants in the study region for human/animal medication; to analyze the human medicinal and veterinary use areas in the context of the remedy groups; to qualitatively compare the results with relevant historical publications; and to compare the intensity and purpose of use between the remedy groups.

Methods

During field studies 134 semi-structured interviews were conducted with locals from 11 villages in the Liubań district of Belarus. Currently used home-remedies as well as those used in the past were documented by employing the folk history method. The subject was approached through health-related uses, not by way of remedies. Interview records were digitalized and structured in Detailed Use Records in order to ascertain local perceptions. An Informant Consensus Factor (FIC) was calculated for remedy groups as well as for different use categories.

Results

In the human medication area the use of nearby remedies was neither very diverse nor numerous: 266 DUR for 45 taxa belonging to 27 families were recorded for cultivated plants along with 188 DUR for 58 different non-plant remedies. The FIC values for both remedy groups were lower than for wild plants. In the ethnoveterinary medicine use area there were 48 DUR referring to the use of 14 cultivated plant taxa from 12 families and 72 DUR referring to the use of 31 non-plant remedies. The FIC value for the whole veterinary use area of cultivated plants was relatively low, yet similar to the FIC of wild plants.

Conclusions

Differences between remedy groups were pronounced, indicating that in domestic human medicine cultivated plants and non-plant remedies are either remarkably less important than wild ones or not considered worth talking about. In ethnoveterinary medicine non-plant remedies are almost equally important as wild plants, while cultivated plants are the least used. People in study area seem to still more often rely on, or are more willing to talk to strangers about, wild plants, as promoted by both official medicine and popular literature.

     

Distinct biological effects of different nanoparticles commonly used in cosmetics and medicine coatings

Background

Metal oxides in nanoparticle form such as zinc oxide and titanium dioxide now appear on the ingredient lists of household products as common and diverse as cosmetics, sunscreens, toothpaste, and medicine. Previous studies of zinc oxide and titanium dioxide in non-nanoparticle format using animals have found few adverse effects. This has led the FDA to classify zinc oxide as GRAS (generally recognized as safe) for use as a food additive. However, there is no regulation specific for the use of these chemicals in nanoparticle format. Recent studies, however, have begun to raise concerns over the pervasive use of these compounds in nanoparticle forms. Unfortunately, there is a lack of easily-adaptable screening methods that would allow for the detection of their biological effects.

Results

We adapted two image-based assays, a fluorescence resonance energy transfer-based caspase activation assay and a green fluorescent protein coupled-LC3 assay, to test for the biological effects of different nanoparticles in a high-throughput format. We show that zinc oxide nanoparticles are cytotoxic. We also show that titanium dioxide nanoparticles are highly effective in inducing autophagy, a cellular disposal mechanism that is often activated when the cell is under stress.

Conclusion

We suggest that these image-based assays provide a method of screening for the biological effects of similar compounds that is both efficient and sensitive as well as do not involve the use of animals.     

Ecological Flexibility as Measured by the Use of Pioneer and Exotic Plants by Two Lemurids: <Emphasis Type="BoldItalic">Eulemur collaris</Emphasis> and <Emphasis Type="BoldItalic">Hapalemur meridionalis</Emphasis>

Primate responses to habitat alteration vary depending on the species’ dietary guild and forest type. Leaves from secondary vegetation can provide nutritious resources to folivorous primates, whereas frugivores, burdened with a scattered spatial and temporal distribution of fruiting resources, require larger home ranges, potentially limiting their ability to cope with altered landscapes. Within coastal southeastern Madagascar, we sought to determine whether two lemur species occupying contrasting ecological niches respond differently to the changing features of their degraded and fragmented habitat. We conducted behavioral observations between 2011 and 2013 on frugivorous collared brown lemurs (Eulemur collaris) and folivorous southern bamboo lemurs (Hapalemur meridionalis). To estimate the ability of lemurs to use pioneer species, we categorized all plants used for feeding and resting as fast growing, mid-growing, or slow growing. We fitted general linear mixed-effects models, one for each plant growth category with monthly proportional use rates as the dependent variable, and included species (E. collaris and H. meridionalis), activity (feeding and resting), and season (dry and wet) as fixed effects. Our results show that E. collaris used both slow- and mid-growing plant species most often, while H. meridionalis were more likely to use fast-growing plants, which indicated an ability to use secondary/disturbed vegetation. Frugivorous E. collaris appear more limited by climax plants, while folivorous H. meridionalis appear to be slightly more adaptable, a finding that is consistent with that for other primate folivores.     

The potential to use QSAR to populate ecotoxicity characterisation factors for simplified LCIA and chemical prioritisation

Purpose

Today’s chemical society use and emit an enormous number of different, potentially ecotoxic, chemicals to the environment. The vast majority of substances do not have characterisation factors describing their ecotoxicity potential. A first stage, high throughput, screening tool is needed for prioritisation of which substances need further measures.

Methods

USEtox characterisation factors were calculated in this work based on data generated by quantitative structure-activity relationship (QSAR) models to expand substance coverage where characterisation factors were missing. Existing QSAR models for physico-chemical data and ecotoxicity were used, and to further fill data gaps, an algae QSAR model was developed. The existing USEtox characterisation factors were used as reference to evaluate the impact from the use of QSARs to generate input data to USEtox, with focus on ecotoxicity data. An inventory of chemicals that make up the Swedish societal stock of plastic additives, and their associated predicted emissions, was used as a case study to rank chemicals according to their ecotoxicity potential.

Results and discussion

For the 210 chemicals in the inventory, only 41 had characterisation factors in the USEtox database. With the use of QSAR generated substance data, an additional 89 characterisation factors could be calculated, substantially improving substance coverage in the ranking. The choice of QSAR model was shown to be important for the reliability of the results, but also with the best correlated model results, the discrepancies between characterisation factors based on estimated data and experimental data were very large.

Conclusions

The use of QSAR estimated data as basis for calculation of characterisation factors, and the further use of those factors for ranking based on ecotoxicity potential, was assessed as a feasible way to gather substance data for large datasets. However, further research and development of the guidance on how to make use of estimated data is needed to achieve improvement of the accuracy of the results.

     

The uses of Kenyan aloes: an analysis of implications for names,distribution and conservation

Background

The genus Aloe is renowned for its medicinal and cosmetic properties and long history of use. Sixty-three Aloe species occur in Kenya, of which around 50 % are endemic. Several species of aloes are threatened with extinction and knowledge about their use is of major importance for sound conservation strategies. The main aims of this study were to assess the biocultural value of Aloe in Kenya by documenting local uses of aloes and evaluating how the vernacular names reflect the relative importance in different ethnic groups.

Methods

Ethnobotanical and ethnotaxonomical data were collected using field observations and semi-structured interviews. Information was collected by interviewing 63 respondents from nine different ethnic groups, representing different ages, gender and occupations. Statistical analyses were performed using R version 3.1.2.

Results

A total of 19 species of Aloe were found in the study area, of which 16 were used. On the generic level Aloe was easily distinguished. At species level, the local and scientific delimitation were almost identical for frequently used taxa. Aloe secundiflora, with 57 unique use records was the most important species. The two most frequently mentioned Aloe treatments, were malaria and poultry diseases. In our study area neither age nor gender had a significant influence on the level of knowledge of Aloe use. Finally, no correlation was found between extent of use and people’s perception of decrease in local aloe populations. The aloes are highly appreciated and are therefore propagated and transported over large areas when people relocate.

Conclusion

Biocultural value is reflected in the ethnotaxonomy of Aloe in Kenya. Different ethnic groups recognise their most-valued Aloe at the genus level as “the aloe” and add explanatory names for the other species, such as the “spotted aloe” and the “one-legged aloe”. Widespread species of Aloe have the highest number of uses. There is no obvious correlation with high use and decrease in abundance of aloes locally, and we found no compelling evidence for local uses causing devastating damage to populations of the 19 species in use, whereas habitat loss and commercial harvesting appear to be of urgent concern for these important plants.

     

Boric Acid and Commercial Organoboron Products as Inhibitors of Drug-Resistant <Emphasis Type="Italic">Candida albicans</Emphasis>

Clinical use of boric acid as a topical antifungal in women who have failed standard antifungal therapy with azole drugs has been used sporadically for decades. Our previous in vitro work showing inhibition of Candida albicans growth was conducted on clinical isolates without antifungal drug susceptibility profiling. Here, we report that boric acid restricts growth of drug-resistant Candida albicans and inhibits hyphal growth and diminishes cell volume. The availability of over-the-counter organoboron compounds intended for use as oral nutritional supplements led us to determine if these also were inhibitory toward resistant Candida and show here that they also possess antifungal activity. Candida glabrata was also found to be inhibited by boric acid and organoboron compounds. Further development of organoboron compounds as topical therapeutics is of potential value.     

Evaluating the effects of chemical exposures on adaptive functioning

• 1.1. Although morphological and classical toxicological data have typically served as criteria for judging the effects of chemicals on the nervous system, there has been increasing interest in the use of behavioral end-points for examining the adverse effects of chemicals on nervous system function.
• 2.2. The present paper describes the current use of behavioral methods in neurotoxicity assessment and surveys some of the recent developments in the use of specialized methods for examining motor, sensory and cognitive changes following chemical exposures.

     

GelJ – a tool for analyzing DNA fingerprint gel images

Background

DNA fingerprinting is a technique for comparing DNA patterns that has applications in a wide variety of contexts. Several commercial and freely-available tools can be used to analyze DNA fingerprint gel images; however, commercial tools are expensive and usually difficult to use; and, free tools support the basic functionality for DNA fingerprint analysis, but lack some instrumental features to obtain accurate results.

Results

In this paper, we present GelJ, a feather-weight, user-friendly, platform-independent, open-source and free tool for analyzing DNA fingerprint gel images. Some of the outstanding features of GelJ are mechanisms for accurate lane- and band-detection, several options for computing migration models, a number of band- and curve-based similarity methods, different techniques for generating dendrograms, comparison of banding patterns from different experiments, and database support.

Conclusions

GelJ is an easy to use tool for analyzing DNA fingerprint gel images. It combines the best characteristics of both free and commercial tools: GelJ is light and simple to use (as free programs), but it also includes the necessary features to obtain precise results (as commercial programs). In addition, GelJ incorporates new functionality that is not supported by any other tool.

     

Comparing land use impacts using ecosystem quality,biogenic carbon emissions,and restoration costs in a case study of hydropower plants in Norway

Purpose

Habitat destruction is today the most severe threat to global biodiversity. Despite decades of efforts, there is still no proper methodology on how to assess all aspects of impacts on biodiversity from land use and land use changes (LULUC) in life cycle analysis (LCA). A majority of LCA studies on land extensive activities still do not include LULUC. In this study, we test different approaches for assessing the impact of land use and land use change related to hydropower for use in LCA and introduce restoration cost as a new approach.

Methods

We assessed four hydropower plant projects in planning phase (two upgrading plants with reservoir and two new run-of-river plants) in Southern Norway with comparable geography, biodiversity, and annual energy production capacity. LULUC was calculated for each habitat type, based on mapping of present and future land use, and was further allocated to energy production for each power plant. Three different approaches to assess land use impact were included: ecosystem scarcity/vulnerability, biogenic greenhouse gas (bGHG) emissions, and the cost of restoring affected habitats. Restoration cost represents a novel approach to LCA for measuring impact of LULUC.

Results and discussion

Overall, the three approaches give similar rankings of impacts: larger impact for small and new power plants and less for larger and expanding existing plants. Reservoirs caused a larger total area affected. Permanent infrastructure has a more similar absolute impact for run-of-river and reservoir-based hydropower, and consequently give relatively larger impact for smaller run-of-river hydropower. All approaches reveal impacts on wetland ecosystems as most important relative to other ecosystems. The methods used for all three approaches would benefit from higher resolution data on land use, habitats, and soil types. Total restoration cost is not accurate, due to uncertainty of offset ratios, but relative restoration costs may still be used to rank restoration alternatives and compare them to the costs of biodiversity offsets.

Conclusions

The different approaches assess different aspects of land use impacts, but they all show large variation of impact between the studied hydropower plants, which shows the importance of including LULUC in LCA for hydropower projects. Improved data of total restoration cost (and cost accounting) are needed to implement this approach in future LCA.

     

UNEP-SETAC guideline on global land use impact assessment on biodiversity and ecosystem services in LCA

Purpose

As a consequence of the multi-functionality of land, the impact assessment of land use in Life Cycle Impact Assessment requires the modelling of several impact pathways covering biodiversity and ecosystem services. To provide consistency amongst these separate impact pathways, general principles for their modelling are provided in this paper. These are refinements to the principles that have already been proposed in publications by the UNEP-SETAC Life Cycle Initiative. In particular, this paper addresses the calculation of land use interventions and land use impacts, the issue of impact reversibility, the spatial and temporal distribution of such impacts and the assessment of absolute or relative ecosystem quality changes. Based on this, we propose a guideline to build methods for land use impact assessment in Life Cycle Assessment (LCA).

Results

Recommendations are given for the development of new characterization models and for which a series of key elements should explicitly be stated, such as the modelled land use impact pathways, the land use/cover typology covered, the level of biogeographical differentiation used for the characterization factors, the reference land use situation used and if relative or absolute quality changes are used to calculate land use impacts. Moreover, for an application of the characterisation factors (CFs) in an LCA study, data collection should be transparent with respect to the data input required from the land use inventory and the regeneration times. Indications on how generic CFs can be used for the background system as well as how spatial-based CFs can be calculated for the foreground system in a specific LCA study and how land use change is to be allocated should be detailed. Finally, it becomes necessary to justify the modelling period for which land use impacts of land transformation and occupation are calculated and how uncertainty is accounted for.

Discussion

The presented guideline is based on a number of assumptions: Discrete land use types are sufficient for an assessment of land use impacts; ecosystem quality remains constant over time of occupation; time and area of occupation are substitutable; transformation time is negligible; regeneration is linear and independent from land use history and landscape configuration; biodiversity and multiple ecosystem services are independent; the ecological impact is linearly increasing with the intervention; and there is no interaction between land use and other drivers such as climate change. These assumptions might influence the results of land use Life Cycle Impact Assessment and need to be critically reflected.

Conclusions and recommendations

In this and the other papers of the special issue, we presented the principles and recommendations for the calculation of land use impacts on biodiversity and ecosystem services on a global scale. In the framework of LCA, they are mainly used for the assessment of land use impacts in the background system. The main areas for further development are the link to regional ecological models running in the foreground system, relative weighting of the ecosystem services midpoints and indirect land use.