Sequence signature analysis of chromosome identity in three Drosophila species

BACKGROUND: All eukaryotic organisms need to distinguish each of their chromosomes. A few protein complexes have been described that recognise entire, specific chromosomes, for instance dosage compensation complexes and the recently discovered autosome-specific Painting of Fourth (POF) protein in Drosophila. However, no sequences have been found that are chromosome-specific and distributed over the entire length of the respective chromosome. Here, we present a new, unbiased, exhaustive computational method that was used to probe three Drosophila genomes for chromosome-specific sequences. RESULTS: By combining genome annotations and cytological data with multivariate statistics related to three Drosophila genomes we found sequence signatures that distinguish Muller's F-elements (chromosome 4 in D. melanogaster) from all other chromosomes in Drosophila that are not attributable to differences in nucleotide composition, simple sequence repeats or repeated elements. Based on these signatures we identified complex motifs that are strongly overrepresented in the F-elements and found indications that the D. melanogaster motif may be involved in POF-binding to the F-element. In addition, the X-chromosomes of D. melanogaster and D. yakuba can be distinguished from the other chromosomes, albeit to a lesser extent. Surprisingly, the conservation of the F-element sequence signatures extends not only between species separated by approximately 55 Myr, but also linearly along the sequenced part of the F-elements. CONCLUSION: Our results suggest that chromosome-distinguishing features are not exclusive to the sex chromosomes, but are also present on at least one autosome (the F-element) in Drosophila

A global view of protein expression in human cells, tissues, and organs

Defining the protein profiles of tissues and organs is critical to understanding the unique characteristics of the various cell types in the human body. In this study, we report on an anatomically comprehensive analysis of 4842 protein profiles in 48 human tissues and 45 human cell lines. A detailed analysis of over 2 million manually annotated, high-resolution, immunohistochemistry-based images showed a high fraction (>65%) of expressed proteins in most cells and tissues, with very few proteins (<2%) detected in any single cell type. Similarly, confocal microscopy in three human cell lines detected expression of more than 70% of the analyzed proteins. Despite this ubiquitous expression, hierarchical clustering analysis, based on global protein expression patterns, shows that the analyzed cells can be still subdivided into groups according to the current concepts of histology and cellular differentiation. This study suggests that tissue specificity is achieved by precise regulation of protein levels in space and time, and that different tissues in the body acquire their unique characteristics by controlling not which proteins are expressed but how much of each is produced

Seeking excellence in end-of-life care (SEECare UK): A UK multi-centred service evaluation

Context People dying in hospitals without specialist palliative care (SPC) input may suffer with significant unmet needs, unrecognised until case-note audit after death. Objectives To evaluate the care of dying hospital inpatients unknown to SPC services across the United Kingdom to better understand their needs and identify factors impacting care of this cohort. Methods Prospective one day UK-wide service evaluation including all dying adult inpatients, excluding those in Emergency Departments/Intensive Care Units. Holistic needs and use of recognised end-of-life care plans (EOLCP) were assessed for those unknown to SPC. Results 88 hospitals, 284 patients. Nearly all patients had unmet holistic needs (93%) which included physical symptoms (75%) and psychological, social and spiritual needs (86%). A dying patient was more likely to have unmet needs and require SPC intervention at a District General Hospital (DGH) compared to a Teaching Hospital/Cancer Centre (Unmet need 98.1% v 91.2% p0.02; Intervention 70.9% v 50.8% p0.001) and when an EOLCP was not utilised (Unmet need 98.3% v 90.3% p0.006; Intervention 67.2% v 53.3% p0.02). Multivariable analyses demonstrated that teaching/cancer hospitals (aOR 0.44 CI 0.26–0.73) and increased SPC medical staffing (aOR 1.69 CI 1.04–2.79) independently influenced need for intervention. However, integration of the use of an EOLCP within the model reduced the impact of SPC medical staffing. Conclusion People dying in hospitals unknown to SPC have significant unmet needs. Further evaluation is required to understand the relationships between patient, staff and service factors in best meeting dying peoples’ needs. The effective content and implementation of EOLCP warrants further investigation

Risk of endometrial cancer in relationship to cigarette smoking: results from the EPIC study

Abstract is not availabl

Fruit and vegetable consumption and lung cancer risk: updated information from the European Prospective Investigation into Cancer and Nutrition (EPIC)

The association of fruit and vegetable consumption and lung cancer incidence was evaluated using the most recent data from the European Prospective Investigation into Cancer and Nutrition (EPIC), applying a refined statistical approach (calibration) to account for measurement error potentially introduced by using food frequency questionnaire data. Between 1992 and 2000, detailed information on diet and life-style of 478,590 individuals participating in EPIC was collected. During a median follow-up of 6.4 years, 1,126 lung cancer cases were observed. Multivariate Cox proportional hazard models were applied for statistical evaluation. In the whole study population, fruit consumption was significantly inversely associated with lung cancer risk while no association was found for vegetable consumption. In current smokers, however, lung cancer risk significantly decreased with higher vegetable consumption; this association became more pronounced after calibration, the hazard ratio (HR) being 0.78 (95% CI 0.620.98) per 100 g increase in daily vegetable consumption. In comparison, the HR per 100 g fruit was 0.92 (0.85-0.99) in the entire cohort and 0.90 (0.81-0.99) in smokers. Exclusion of cases diagnosed during the first 2 years of follow-up strengthened these associations, the HR being 0.71 (0.55-0.94) for vegetables (smokers) and 0.86 (0.78-0.95) for fruit (entire cohort). Cancer incidence decreased with higher consumption of apples and pears (entire cohort) as well as root vegetables (smokers). In addition to an overall inverse association with fruit intake, the results of this evaluation add evidence for a significant inverse association of vegetable consumption and lung cancer incidence in smokers. (C) 2007 Wiley-Liss, Inc

Minimum Information about T Regulatory Cells: A Step toward Reproducibility and Standardization.

Cellular therapies with CD4+ T regulatory cells (Tregs) hold promise of efficacious treatment for the variety of autoimmune and allergic diseases as well as posttransplant complications. Nevertheless, current manufacturing of Tregs as a cellular medicinal product varies between different laboratories, which in turn hampers precise comparisons of the results between the studies performed. While the number of clinical trials testing Tregs is already substantial, it seems to be crucial to provide some standardized characteristics of Treg products in order to minimize the problem. We have previously developed reporting guidelines called minimum information about tolerogenic antigen-presenting cells, which allows the comparison between different preparations of tolerance-inducing antigen-presenting cells. Having this experience, here we describe another minimum information about Tregs (MITREG). It is important to note that MITREG does not dictate how investigators should generate or characterize Tregs, but it does require investigators to report their Treg data in a consistent and transparent manner. We hope this will, therefore, be a useful tool facilitating standardized reporting on the manufacturing of Tregs, either for research purposes or for clinical application. This way MITREG might also be an important step toward more standardized and reproducible testing of the Tregs preparations in clinical applications

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Är LIS svaret på en levande landsbygd? : En kvalitativ studie av Örnsköldsviks landsbygdsutveckling

The purpose of this study is to investigate how the municipality Örnsköldsvik is working with rural development as a whole and in the four geographical BYGDSAM-areas. The study will also investigate how the outcome of the municipality’s designated areas for exemption of the shoreline protection, also called rural development in shoreline locations, has developed within the last ten years. To do this a qualitative study has been done in form of six interviews. Four of the respondents are representants for each BYGDSAM-area and two respondents represents the municipality where one works with rural development and the other one works with rural development in shoreline locations. The municipality Örnsköldsvik is working with rural development from several different approaches. They have a rural development strategy as an addition to their overview plan, they also have a thematic supplement for rural development in shoreline locations. BYGDSAM – the country in collaboration was formed in 2017 as a long-term solution for the rural development on the countryside. Örnsköldsviks municipality has a diversified land use with large nature resources and therefore also scattered rural problems. The rural countryside differs if the location is near the coastline and the city Örnsköldsvik or inland in the country. The inner parts of the municipality are facing problems like disused service in form of schools shutting down and a lack of nursing homes. The areas that are located near the coast and the city Örnsköldsvik are facing other problems like a lack of houses and plots to build on. These areas also have an increase in housing prices because they are more attractive to move to. One of the tools to work with rural development is – rural development in shoreline locations. This tool gives municipalities opportunity to point out areas in shoreline locations that are suitable for settlement. None of the respondents that was interviewed for the study could comment on that settlement had taken place within such an area during the last ten years in Örnsköldsviks municipality. But this tool in rural planning is complicated. The legislation that prevails now, makes it hard for municipalities in Sweden to point out areas where exemptions from the shoreline protection can be applied. The municipalities “must almost guess” where attractive areas for settlement is right now or are going to be in the future. The legalisation on shoreline protection applies to all water, without taking the locations diversity into consideration. In 2019 the government put down a suggestion saying that the shoreline protection should be rebuilt from the ground up. The survey was done in 2020 and the suggestion is going to be displayed in 2021. The changes were supposed to make development on the countryside easier, but what so far has been exhibited is that this may not be the case and therefore no major changes are expected to occur in the shoreline protection

Är LIS svaret på en levande landsbygd? : En kvalitativ studie av Örnsköldsviks landsbygdsutveckling

The purpose of this study is to investigate how the municipality Örnsköldsvik is working with rural development as a whole and in the four geographical BYGDSAM-areas. The study will also investigate how the outcome of the municipality’s designated areas for exemption of the shoreline protection, also called rural development in shoreline locations, has developed within the last ten years. To do this a qualitative study has been done in form of six interviews. Four of the respondents are representants for each BYGDSAM-area and two respondents represents the municipality where one works with rural development and the other one works with rural development in shoreline locations. The municipality Örnsköldsvik is working with rural development from several different approaches. They have a rural development strategy as an addition to their overview plan, they also have a thematic supplement for rural development in shoreline locations. BYGDSAM – the country in collaboration was formed in 2017 as a long-term solution for the rural development on the countryside. Örnsköldsviks municipality has a diversified land use with large nature resources and therefore also scattered rural problems. The rural countryside differs if the location is near the coastline and the city Örnsköldsvik or inland in the country. The inner parts of the municipality are facing problems like disused service in form of schools shutting down and a lack of nursing homes. The areas that are located near the coast and the city Örnsköldsvik are facing other problems like a lack of houses and plots to build on. These areas also have an increase in housing prices because they are more attractive to move to. One of the tools to work with rural development is – rural development in shoreline locations. This tool gives municipalities opportunity to point out areas in shoreline locations that are suitable for settlement. None of the respondents that was interviewed for the study could comment on that settlement had taken place within such an area during the last ten years in Örnsköldsviks municipality. But this tool in rural planning is complicated. The legislation that prevails now, makes it hard for municipalities in Sweden to point out areas where exemptions from the shoreline protection can be applied. The municipalities “must almost guess” where attractive areas for settlement is right now or are going to be in the future. The legalisation on shoreline protection applies to all water, without taking the locations diversity into consideration. In 2019 the government put down a suggestion saying that the shoreline protection should be rebuilt from the ground up. The survey was done in 2020 and the suggestion is going to be displayed in 2021. The changes were supposed to make development on the countryside easier, but what so far has been exhibited is that this may not be the case and therefore no major changes are expected to occur in the shoreline protection