Systematic bioinformatic analysis of expression levels of 17,330 human genes across 9,783 samples from 175 types of healthy and pathological tissues

Our knowledge on tissue- and disease-specific functions of human genes is rather limited and highly context-specific. Here, we have developed a method for the comparison of mRNA expression levels of most human genes across 9,783 Affymetrix gene expression array experiments representing 43 normal human tissue types, 68 cancer types, and 64 other diseases. This database of gene expression patterns in normal human tissues and pathological conditions covers 113 million datapoints and is available from the GeneSapiens website

GTI: A Novel Algorithm for Identifying Outlier Gene Expression Profiles from Integrated Microarray Datasets

Background Meta-analysis of gene expression microarray datasets presents significant challenges for statistical analysis. We developed and validated a new bioinformatic method for the identification of genes upregulated in subsets of samples of a given tumour type (‘outlier genes’), a hallmark of potential oncogenes. Methodology A new statistical method (the gene tissue index, GTI) was developed by modifying and adapting algorithms originally developed for statistical problems in economics. We compared the potential of the GTI to detect outlier genes in meta-datasets with four previously defined statistical methods, COPA, the OS statistic, the t-test and ORT, using simulated data. We demonstrated that the GTI performed equally well to existing methods in a single study simulation. Next, we evaluated the performance of the GTI in the analysis of combined Affymetrix gene expression data from several published studies covering 392 normal samples of tissue from the central nervous system, 74 astrocytomas, and 353 glioblastomas. According to the results, the GTI was better able than most of the previous methods to identify known oncogenic outlier genes. In addition, the GTI identified 29 novel outlier genes in glioblastomas, including TYMS and CDKN2A. The over-expression of these genes was validated in vivo by immunohistochemical staining data from clinical glioblastoma samples. Immunohistochemical data were available for 65% (19 of 29) of these genes, and 17 of these 19 genes (90%) showed a typical outlier staining pattern. Furthermore, raltitrexed, a specific inhibitor of TYMS used in the therapy of tumour types other than glioblastoma, also effectively blocked cell proliferation in glioblastoma cell lines, thus highlighting this outlier gene candidate as a potential therapeutic target. Conclusions/Significance Taken together, these results support the GTI as a novel approach to identify potential oncogene outliers and drug targets. The algorithm is implemented in an R package (Text S1).Peer reviewe

Being lesbian – does the doctor need to know?: A qualitative study about the significance of disclosure in general practice

Lesbian women make up a sexual minority within a heteronormative society where homosexuality becomes invisible and inferior. Minority stress is the excess stress individuals from stigmatized social categories experience because of their minority position. Stress may influence health and identity. It is not the burden of stress itself that determines its influence on health and identity, but how the individual copes with the stress. Existing research indicates that having a lesbian orientation may be especially challenging in encounters with health care professionals. Consequently, we wanted to explore how minority stress may be experienced by lesbian women in Norway today, and what strategies they employ to cope successfully with these situations. We wanted particularly to learn how minority stress comes into play within the health care system. The objective of this thesis is to develop knowledge that may be applied as a foundation for quality care and improved health for lesbian women, with a special relevance for general practice. We have accomplished three sub-studies based on experiences of lesbian women to illuminate the following issues: 1) What does it mean to lesbian women that the general practitioner is aware of their sexual orientation? 2) What kind of experiences related to sexual orientation do Norwegian lesbian women report from encounters with health care professionals? 3) Which strategies do lesbian women use to cope with challenges related to sexual orientation in their every-day lives? In sub-study I we conducted a focus group interview with lesbian women focusing on when and why it may be important to inform the general practitioner about their sexual orientation. We gathered data in the form of web based histories for substudies II and III. The empirical data consisted of 128 histories about concrete experiences in health care encounters where the lesbian orientation was of importance (II), and 64 histories about successful coping experiences related to the lesbian orientation (III). Data were analyzed with systematic text condensation in all three sub-studies. The analysis was data-driven and supported by theories of heteronormativity (I and II) and salutogenesis and coping (III). The analysis in sub-study I demonstrated that informing the general practitioner about the lesbian orientation may be important in order to be able to be oneself and communicate freely, and it may be relevant for the medical problem at hand. The experiences of the participants constitute a foundation for knowledge about how doctors may support the coming-out process of lesbian women. Sub-study II presents a wide range of experiences among lesbian women encountering health care professionals. The analysis concludes that for health care professionals a persistent awareness that not all patients are heterosexual, a positive attitude to lesbian orientation, and knowledge about lesbian-specific health matters, are required to offer health care services of high quality to lesbian patients. The challenges described by the participants in sub-study III concerned the question of whether or not disclose the lesbian orientation, how to disclose, how to handle derogatory remarks or actions, and how to face homo-negativity within family and other significant relations. Positive coping experiences comprised openness about the lesbian orientation, the way disclosure was carried out, and to maintain dignity when prejudice was encountered. Dignity could be maintained by demanding respect or arguing for rights, or by boosting thoughts and feelings that it is good to be lesbian. The analysis demonstrates that lesbian self-confidence – a personal conviction that a lesbian orientation is equally good and natural as a heterosexual orientation – may be a prerequisite for the positive coping strategies. The thesis presents these main findings: Lesbian women must continually deal with how to appear. Disclosure competency may improve lesbian women’s coping of minority stress related to openness. Lesbian women must continually receive and process reactions from the surroundings. Dignity may be maintained in all situations by sustaining and communicating lesbian self-confidence. Even in Norway 2012 do lesbian women experience minority stress that calls for coping strategies. Lesbian self-confidence may strengthen resilience against minority stress

Herbivore diversity effects on Arctic tundra ecosystems : a systematic review

Background: Northern ecosystems are strongly influenced by herbivores that differ in their impacts on the ecosystem. Yet the role of herbivore diversity in shaping the structure and functioning of tundra ecosystems has been overlooked. With climate and land-use changes causing rapid shifts in Arctic species assemblages, a better understanding of the consequences of herbivore diversity changes for tundra ecosystem functioning is urgently needed. This systematic review synthesizes available evidence on the effects of herbivore diversity on different processes, functions, and properties of tundra ecosystems. Methods: Following a published protocol, our systematic review combined primary field studies retrieved from bibliographic databases, search engines and specialist websites that compared tundra ecosystem responses to different levels of vertebrate and invertebrate herbivore diversity. We used the number of functional groups of herbivores (i.e., functional group richness) as a measure of the diversity of the herbivore assemblage. We screened titles, abstracts, and full texts of studies using pre-defined eligibility criteria. We critically appraised the validity of the studies, tested the influence of different moderators, and conducted sensitivity analyses. Quantitative synthesis (i.e., calculation of effect sizes) was performed for ecosystem responses reported by at least five articles and meta-regressions including the effects of potential modifiers for those reported by at least 10 articles. Review findings: The literature searches retrieved 5944 articles. After screening titles, abstracts, and full texts, 201 articles including 3713 studies (i.e., individual comparisons) were deemed relevant for the systematic review, with 2844 of these studies included in quantitative syntheses. The available evidence base on the effects of herbivore diversity on tundra ecosystems is concentrated around well-established research locations and focuses mainly on the impacts of vertebrate herbivores on vegetation. Overall, greater herbivore diversity led to increased abundance of feeding marks by herbivores and soil temperature, and to reduced total abundance of plants, graminoids, forbs, and litter, plant leaf size, plant height, and moss depth, but the effects of herbivore diversity were difficult to tease apart from those of excluding vertebrate herbivores. The effects of different functional groups of herbivores on graminoid and lichen abundance compensated each other, leading to no net effects when herbivore effects were combined. In turn, smaller herbivores and large-bodied herbivores only reduced plant height when occurring together but not when occurring separately. Greater herbivore diversity increased plant diversity in graminoid tundra but not in other habitat types. Conclusions: This systematic review underscores the importance of herbivore diversity in shaping the structure and function of Arctic ecosystems, with different functional groups of herbivores exerting additive or compensatory effects that can be modulated by environmental conditions. Still, many challenges remain to fully understand the complex impacts of herbivore diversity on tundra ecosystems. Future studies should explicitly address the role of herbivore diversity beyond presence-absence, targeting a broader range of ecosystem responses and explicitly including invertebrate herbivores. A better understanding of the role of herbivore diversity will enhance our ability to predict whether and where shifts in herbivore assemblages might mitigate or further amplify the impacts of environmental change on Arctic ecosystems

Herbivore diversity effects on Arctic tundra ecosystems: a systematic review

Abstract Background Northern ecosystems are strongly influenced by herbivores that differ in their impacts on the ecosystem. Yet the role of herbivore diversity in shaping the structure and functioning of tundra ecosystems has been overlooked. With climate and land-use changes causing rapid shifts in Arctic species assemblages, a better understanding of the consequences of herbivore diversity changes for tundra ecosystem functioning is urgently needed. This systematic review synthesizes available evidence on the effects of herbivore diversity on different processes, functions, and properties of tundra ecosystems. Methods Following a published protocol, our systematic review combined primary field studies retrieved from bibliographic databases, search engines and specialist websites that compared tundra ecosystem responses to different levels of vertebrate and invertebrate herbivore diversity. We used the number of functional groups of herbivores (i.e., functional group richness) as a measure of the diversity of the herbivore assemblage. We screened titles, abstracts, and full texts of studies using pre-defined eligibility criteria. We critically appraised the validity of the studies, tested the influence of different moderators, and conducted sensitivity analyses. Quantitative synthesis (i.e., calculation of effect sizes) was performed for ecosystem responses reported by at least five articles and meta-regressions including the effects of potential modifiers for those reported by at least 10 articles. Review findings The literature searches retrieved 5944 articles. After screening titles, abstracts, and full texts, 201 articles including 3713 studies (i.e., individual comparisons) were deemed relevant for the systematic review, with 2844 of these studies included in quantitative syntheses. The available evidence base on the effects of herbivore diversity on tundra ecosystems is concentrated around well-established research locations and focuses mainly on the impacts of vertebrate herbivores on vegetation. Overall, greater herbivore diversity led to increased abundance of feeding marks by herbivores and soil temperature, and to reduced total abundance of plants, graminoids, forbs, and litter, plant leaf size, plant height, and moss depth, but the effects of herbivore diversity were difficult to tease apart from those of excluding vertebrate herbivores. The effects of different functional groups of herbivores on graminoid and lichen abundance compensated each other, leading to no net effects when herbivore effects were combined. In turn, smaller herbivores and large-bodied herbivores only reduced plant height when occurring together but not when occurring separately. Greater herbivore diversity increased plant diversity in graminoid tundra but not in other habitat types. Conclusions This systematic review underscores the importance of herbivore diversity in shaping the structure and function of Arctic ecosystems, with different functional groups of herbivores exerting additive or compensatory effects that can be modulated by environmental conditions. Still, many challenges remain to fully understand the complex impacts of herbivore diversity on tundra ecosystems. Future studies should explicitly address the role of herbivore diversity beyond presence-absence, targeting a broader range of ecosystem responses and explicitly including invertebrate herbivores. A better understanding of the role of herbivore diversity will enhance our ability to predict whether and where shifts in herbivore assemblages might mitigate or further amplify the impacts of environmental change on Arctic ecosystems. </jats:sec