umu.sePublikationer
Ändra sökning
Avgränsa sökresultatet
1234567 1 - 50 av 642
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1. Abel, Olubunmi
    et al.
    Powell, John F
    Andersen, Peter M
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Al-Chalabi, Ammar
    Credibility analysis of putative disease-causing genes using bioinformatics2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 6, s. e64899-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Genetic studies are challenging in many complex diseases, particularly those with limited diagnostic certainty, low prevalence or of old age. The result is that genes may be reported as disease-causing with varying levels of evidence, and in some cases, the data may be so limited as to be indistinguishable from chance findings. When there are large numbers of such genes, an objective method for ranking the evidence is useful. Using the neurodegenerative and complex disease amyotrophic lateral sclerosis (ALS) as a model, and the disease-specific database ALSoD, the objective is to develop a method using publicly available data to generate a credibility score for putative disease-causing genes.

    Methods: Genes with at least one publication suggesting involvement in adult onset familial ALS were collated following an exhaustive literature search. SQL was used to generate a score by extracting information from the publications and combined with a pathogenicity analysis using bioinformatics tools. The resulting score allowed us to rank genes in order of credibility. To validate the method, we compared the objective ranking with a rank generated by ALS genetics experts. Spearman's Rho was used to compare rankings generated by the different methods.

    Results: The automated method ranked ALS genes in the following order: SOD1, TARDBP, FUS, ANG, SPG11, NEFH, OPTN, ALS2, SETX, FIG4, VAPB, DCTN1, TAF15, VCP, DAO. This compared very well to the ranking of ALS genetics experts, with Spearman's Rho of 0.69 (P = 0.009).

    Conclusion: We have presented an automated method for scoring the level of evidence for a gene being disease-causing. In developing the method we have used the model disease ALS, but it could equally be applied to any disease in which there is genotypic uncertainty.

  • 2. Aboagye, Emmanuel
    et al.
    Hagberg, Jan
    Axén, Iben
    Kwak, Lydia
    Lohela-Karlsson, Malin
    Skillgate, Eva
    Dahlgren, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Yrkes- och miljömedicin.
    Jensen, Irene
    Individual preferences for physical exercise as secondary prevention for non-specific low back pain: a discrete choice experiment2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 12, artikel-id e0187709Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Exercise is effective in improving non-specific low back pain (LBP). Certain components of physical exercise, such as the type, intensity and frequency of exercise, are likely to influence participation among working adults with non-specific LBP, but the value and relative importance of these components remain unknown. The study's aim was to examine such specific components and their influence on individual preferences for exercise for secondary prevention of non-specific LBP among working adults. Methods: In a discrete choice experiment, working individuals with non-specific LBP answered a webbased questionnaire. Each respondent was given ten pairs of hypothetical exercise programs and asked to choose one option from each pair. The choices comprised six attributes of exercise (i.e., type of training, design, intensity, frequency, proximity and incentives), each with either three or four levels. A conditional logit regression that reflected the random utility model was used to analyze the responses. Results: The final study population consisted of 112 participants. The participants' preferred exercise option was aerobic (i.e., cardiovascular) rather than strength training, group exercise with trainer supervision, rather than individual or unsupervised exercise. They also preferred high intensity exercise performed at least once or twice per week. The most popular types of incentive were exercise during working hours and a wellness allowance rather than coupons for sports goods. The results show that the relative value of some attribute levels differed between young adults (age <= 44 years) and older adults (age <= 45 years) in terms of the level of trainer supervision required, exercise intensity, travel time to exercise location and financial incentives. For active study participants, exercise frequency (i.e., twice per week, 1.15; CI: 0.25; 2.06) influenced choice of exercise. For individuals with more than one child, travel time (i.e., 20 minutes, - 0.55; CI: 0.65; 3.26) was also an influential attribute for choice of exercise, showing that people with children at home preferred to exercise close to home. Conclusions: This study adds to our knowledge about what types of exercise working adults with back pain are most likely to participate in. The exercise should be a cardiovascular type of training carried out in a group with trainer supervision. It should also be of high intensity and preferably performed twice per week during working hours. Coupons for sports goods do not appear to motivate physical activity among workers with LBP. The findings of the study could have a substantial impact on the planning and development of exercise provision and promotion strategies to improve non-specific LBP. Providers and employers may be able to improve participation in exercise programs for adults with non-specific LBP by focusing on the exercise components which are the most attractive. This in turn would improve satisfaction and adherence to exercise interventions aimed at preventing recurrent non-specific LBP.

  • 3.
    Abraha, Atakelti
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Tigray Health Bureau, Tigray and Ethiopian Health Insurance Agency, Addis Ababa, Ethiopia.
    Myléus, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Byass, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Institutes of Applied Health Sciences, School of Medicine and Dentistry, University of Aberdeen, United Kingdom; MRC/Wits Rural Public Health and Health Transitions Research Unit, School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
    Kahsay, Asmelash
    Tigray Health Bureau, Tigray and Ethiopian Health Insurance Agency, Addis Ababa, Ethiopia.
    Kinsman, John
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Department of Public Health Sciences, Global Health (IHCAR), Karolinska Institute, Stockholm, Sweden.
    Social determinants of under-5 child health: A qualitative study in Wolkayit Woreda, Tigray Region, Ethiopia2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 6, artikel-id e0218101Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite the significant reductions seen in under-5 child mortality in Ethiopia over the last two decades, more than 10,000 children still die each year in Tigray Region alone, of whom 75% die from preventable diseases. Using an equity lens, this study aimed to investigate the social determinants of child health in one particularly vulnerable district as a means of informing the health policy decision-making process. An exploratory qualitative study design was adopted, combining focus group discussions and qualitative interviews. Seven Focus Group Discussions with mothers of young children, and 21 qualitative interviews with health workers were conducted in Wolkayit district in May-June 2015. Data were subjected to thematic analysis. Mothers’ knowledge regarding the major causes of child mortality appeared to be good, and they also knew about and trusted the available child health interventions. However, utilization and practice of these interventions was limited by a range of issues, including cultural factors, financial shortages, limited female autonomy on financial resources, seasonal mobility, and inaccessible or unaffordable health services. Our findings pointed to the importance of a multi-sectoral strategy to improve child health equity and reduce under-5 mortality in Wolkayit. Recommendations include further decentralizing child health services to local-level Health Posts, and increasing the number of Health Facilities based on local topography and living conditions.

  • 4.
    Adamo, Hanibal Hani
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergström, Sofia Halin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Characterization of a Gene Expression Signature in Normal Rat Prostate Tissue Induced by the Presence of a Tumor Elsewhere in the Organ2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 6, artikel-id e0130076Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating changes in the tumor-bearing organ, for example growth of the vasculature, an altered extracellular matrix, and influx of inflammatory cells. To investigate this response further, we compared prostate morphology and the gene expression profile of tumor-bearing normal rat prostate tissue (termed tumor-instructed/indicating normal tissue (TINT)) with that of prostate tissue from controls. Dunning rat AT-1 prostate cancer cells were injected into rat prostate and tumors were established after 10 days. As controls we used intact animals, animals injected with heat-killed AT-1 cells or cell culture medium. None of the controls showed morphological TINT-changes. A rat Illumina whole-genome expression array was used to analyze gene expression in AT-1 tumors, TINT, and in medium injected prostate tissue. We identified 423 upregulated genes and 38 downregulated genes (p<0.05, >= 2-fold change) in TINT relative to controls. Quantitative RT-PCR analysis verified key TINT-changes, and they were not detected in controls. Expression of some genes was changed in a manner similar to that in the tumor, whereas other changes were exclusive to TINT. Ontological analysis using GeneGo software showed that the TINT gene expression profile was coupled to processes such as inflammation, immune response, and wounding. Many of the genes whose expression is altered in TINT have well-established roles in tumor biology, and the present findings indicate that they may also function by adapting the surrounding tumor-bearing organ to the needs of the tumor. Even though a minor tumor cell contamination in TINT samples cannot be ruled out, our data suggest that there are tumor-induced changes in gene expression in the normal tumor-bearing organ which can probably not be explained by tumor cell contamination. It is important to validate these changes further, as they could hypothetically serve as novel diagnostic and prognostic markers of prostate cancer.

  • 5.
    Adamo, Hanibal Hani
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Strömvall, Kerstin
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Nilsson, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Halin Bergström, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 11, artikel-id e0141601Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues.

  • 6. Agogo, George O.
    et al.
    van der Voet, Hilko
    van't Veer, Pieter
    Ferrari, Pietro
    Leenders, Max
    Muller, David C.
    Sanchez-Cantalejo, Emilio
    Bamia, Christina
    Braaten, Tonje
    Knueppel, Sven
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    van Eeuwijk, Fred A.
    Boshuizen, Hendriek
    Use of Two-Part Regression Calibration Model to Correct for Measurement Error in Episodically Consumed Foods in a Single-Replicate Study Design: EPIC Case Study2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 11, s. e113160-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted twopart regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model.

  • 7.
    Aguilar, Ximena
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Blomberg, Jeanette
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Brännström, Kristoffer
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Olofsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Schleucher, Jurgen
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Björklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Interaction Studies of the Human and Arabidopsis thaliana Med25-ACID Proteins with the Herpes Simplex Virus VP16-and Plant-Specific Dreb2a Transcription Factors2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 5, s. e98575-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mediator is an evolutionary conserved multi-protein complex present in all eukaryotes. It functions as a transcriptional coregulator by conveying signals from activators and repressors to the RNA polymerase II transcription machinery. The Arabidopsis thaliana Med25 (aMed25) ACtivation Interaction Domain (ACID) interacts with the Dreb2a activator which is involved in plant stress response pathways, while Human Med25-ACID (hMed25) interacts with the herpes simplex virus VP16 activator. Despite low sequence similarity, hMed25-ACID also interacts with the plant-specific Dreb2a transcriptional activator protein. We have used GST pull-down-, surface plasmon resonance-, isothermal titration calorimetry and NMR chemical shift experiments to characterize interactions between Dreb2a and VP16, with the hMed25 and aMed25-ACIDs. We found that VP16 interacts with aMed25-ACID with similar affinity as with hMed25-ACID and that the binding surface on aMed25-ACID overlaps with the binding site for Dreb2a. We also show that the Dreb2a interaction region in hMed25-ACID overlaps with the earlier reported VP16 binding site. In addition, we show that hMed25-ACID/Dreb2a and aMed25-ACID/Dreb2a display similar binding affinities but different binding energetics. Our results therefore indicate that interaction between transcriptional regulators and their target proteins in Mediator are less dependent on the primary sequences in the interaction domains but that these domains fold into similar structures upon interaction.

  • 8.
    Ahmad, Irfan
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan.
    Karah, Nabil
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Nadeem, Aftab
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Analysis of colony phase variation switch in Acinetobacter baumannii clinical isolates2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 1, artikel-id e0210082Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Reversible switching between opaque and translucent colony formation is a novel feature of Acinetobacter baumannii that has been associated with variations in the cell morphology, surface motility, biofilm formation, antibiotic resistance and virulence. Here, we assessed a number of phenotypic alterations related to colony switching in A. baumannii clinical isolates belonging to different multi-locus sequence types. Our findings demonstrated that these phenotypic alterations were mostly strain-specific. In general, the translucent subpopulations of A. baumannii produced more dense biofilms, were more piliated, and released larger amounts of outer membrane vesicles (OMVs). In addition, the translucent subpopulations caused reduced fertility of Caenorhabditis elegans. When assessed for effects on the immune response in RAW 264.7 macrophages, the OMVs isolated from opaque subpopulations of A. baumannii appeared to be more immunogenic than the OMVs from the translucent form. However, also the OMVs from the translucent subpopulations had the potential to evoke an immune response. Therefore, we suggest that OMVs may be considered for development of new immunotherapeutic treatments against A. baumannii infections.

  • 9. Al Nimer, Faiez
    et al.
    Thelin, Eric
    Nystrom, Harriet
    Dring, Ann M.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Svenningsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Piehl, Fredrik
    Nelson, David W.
    Bellander, Bo-Michael
    Comparative Assessment of the Prognostic Value of Biomarkers in Traumatic Brain Injury Reveals an Independent Role for Serum Levels of Neurofilament Light2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 7, artikel-id e0132177Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Traumatic brain injury (TBI) is a common cause of death and disability, worldwide. Early determination of injury severity is essential to improve care. Neurofilament light (NF-L) has been introduced as a marker of neuroaxonal injury in neuroinflammatory/-degenerative diseases. In this study we determined the predictive power of serum (s-) and cerebrospinal fluid (CSF-) NF-L levels towards outcome, and explored their potential correlation to diffuse axonal injury (DAI). A total of 182 patients suffering from TBI admitted to the neurointensive care unit at a level 1 trauma center were included. S-NF-L levels were acquired, together with S100B and neuron-specific enolase (NSE). CSF-NF-L was measured in a subcohort (n = 84) with ventriculostomies. Clinical and neuro-radiological parameters, including computerized tomography (CT) and magnetic resonance imaging, were included in the analyses. Outcome was assessed 6 to 12 months after injury using the Glasgow Outcome Score (1-5). In univariate proportional odds analyses mean s-NF-L, -S100B and -NSE levels presented a pseudo-R-2 Nagelkerke of 0.062, 0.214 and 0.074 in correlation to outcome, respectively. In a multivariate analysis, in addition to a model including core parameters (pseudo-R-2 0.33 towards outcome; Age, Glasgow Coma Scale, pupil response, Stockholm CT score, abbreviated injury severity score, S100B), S-NF-L yielded an extra 0.023 pseudo-R-2 and a significantly better model (p = 0.006) No correlation between DAI or CT assessed-intracranial damage and NF-L was found. Our study thus demonstrates that SNF-L correlates to TBI outcome, even if used in models with S100B, indicating an independent contribution to the prediction, perhaps by reflecting different pathophysiological processes, not possible to monitor using conventional neuroradiology. Although we did not find a predictive value of NF-L for DAI, this cannot be completely excluded. We suggest further

  • 10. Alarcon, Flora
    et al.
    Plante-Bordeneuve, Violaine
    Olsson, Malin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Norrlands university hospital, NUS M31, Umeå, Sweden.
    Nuel, Gregory
    Non-parametric estimation of survival in age-dependent genetic disease and application to the transthyretin-related hereditary amyloidosis2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 9, artikel-id e0203860Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In genetic diseases with variable age of onset, survival function estimation for the mutation carriers as well as estimation of the modifying factors effects are essential to provide individual risk assessment, both for mutation carriers management and prevention strategies. In practice, this survival function is classically estimated from pedigrees data where most genotypes are unobserved. In this article, we present a unifying Expectation-Maximization (EM) framework combining probabilistic computations in Bayesian networks with standard statistical survival procedures in order to provide mutation carrier survival estimates. The proposed approach allows to obtain previously published parametric estimates (e.g. Weibull survival) as particular cases as well as more general Kaplan-Meier non-parametric estimates, which is the main contribution. Note that covariates can also be taken into account using a proportional hazard model. The whole methodology is both validated on simulated data and applied to family samples with transthyretin-related hereditary amyloidosis (a rare autosomal dominant disease with highly variable age of onset), showing very promising results.

  • 11.
    Alex, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Fjellman-Wiklund, Anncristine
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Sjukgymnastik.
    Lundman, Berit
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Christianson, Monica
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Hammarström, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Beyond a Dichotomous View of the Concepts of 'Sex' and 'Gender' Focus Group Discussions among Gender Researchers at a Medical Faculty2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 11, s. e50275-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: The concepts of 'sex' and 'gender' are both of vital importance in medicine and health sciences. However, the meaning of these concepts has seldom been discussed in the medical literature. The aim of this study was to explore what the concepts of 'sex' and 'gender' meant for gender researchers based in a medical faculty. Methods: Sixteen researchers took part in focus group discussions. The analysis was performed in several steps. The participating researchers read the text and discussed ideas for analysis in national and international workshops. The data were analysed using qualitative content analysis. The authors performed independent preliminary analyses, which were further developed and intensively discussed between the authors. Results: The analysis of meanings of the concepts of 'sex' and 'gender' for gender researchers based in a medical faculty resulted in three categories; "Sex as more than biology", with the subcategories 'sex' is not simply biological, 'sex' as classification, and 'sex' as fluid and changeable; "Gender as a multiplicity of power-related constructions", with the subcategories: 'gender' as constructions, 'gender' power dimensions, and 'gender' as doing femininities and masculinities; "'Sex and gender as interwoven", with the subcategories: 'sex' and 'gender' as inseparable and embodying 'sex' and 'gender'. Conclusions: Gender researchers within medicine pointed out the importance of looking beyond a dichotomous view of the concepts of 'sex' and 'gender'. The perception of the concepts was that 'sex' and 'gender' were intertwined. Further research is needed to explore how 'sex' and 'gender' interact.

  • 12.
    Al-Furoukh, Natalie
    et al.
    Department of Cardiac Development and Remodeling, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany.
    Kardon, Julia R
    Krüger, Marcus
    Szibor, Marten
    Baker, Tania A
    Braun, Thomas
    NOA1, a novel ClpXP substrate, takes an unexpected nuclear detour prior to mitochondrial import.2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The mitochondrial matrix GTPase NOA1 is a nuclear encoded protein, essential for mitochondrial protein synthesis, oxidative phosphorylation and ATP production. Here, we demonstrate that newly translated NOA1 protein is imported into the nucleus, where it localizes to the nucleolus and interacts with UBF1 before nuclear export and import into mitochondria. Mutation of the nuclear localization signal (NLS) prevented both nuclear and mitochondrial import while deletion of the N-terminal mitochondrial targeting sequence (MTS) or the C-terminal RNA binding domain of NOA1 impaired mitochondrial import. Absence of the MTS resulted in accumulation of NOA1 in the nucleus and increased caspase-dependent apoptosis. We also found that export of NOA1 from the nucleus requires a leptomycin-B sensitive, Crm1-dependent nuclear export signal (NES). Finally, we show that NOA1 is a new substrate of the mitochondrial matrix protease complex ClpXP. Our results uncovered an unexpected, mandatory detour of NOA1 through the nucleolus before uptake into mitochondria. We propose that nucleo-mitochondrial translocation of proteins is more widespread than previously anticipated providing additional means to control protein bioavailability as well as cellular communication between both compartments.

  • 13.
    Amer, Ayad
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Costa, Tiago
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Farag, Salah
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Avican, Ummehan
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Forsberg, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Francis, Matthew
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Genetically engineered frameshifted YopN-TyeA chimeras influence type III secretion system function in Yersinia pseudotuberculosis2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 10, artikel-id e77767Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Type III secretion is a tightly controlled virulence mechanism utilized by many gram negative bacteria to colonize their eukaryotic hosts. To infect their host, human pathogenic Yersinia spp. translocate protein toxins into the host cell cytosol through a preassembled Ysc-Yop type III secretion device. Several of the Ysc-Yop components are known for their roles in controlling substrate secretion and translocation. Particularly important in this role is the YopN and TyeA heterodimer. In this study, we confirm that Y. pseudotuberculosis naturally produce a 42 kDa YopN-TyeA hybrid protein as a result of a +1 frame shift near the 3 prime of yopN mRNA, as has been previously reported for the closely related Y. pestis. To assess the biological role of this YopN-TyeA hybrid in T3SS by Y. pseudotuberculosis, we used in cis site-directed mutagenesis to engineer bacteria to either produce predominately the YopN-TyeA hybrid by introducing +1 frame shifts to yopN after codon 278 or 287, or to produce only singular YopN and TyeA polypeptides by introducing yopN sequence from Y. enterocolitica, which is known not to produce the hybrid. Significantly, the engineered 42 kDa YopN-TyeA fusions were abundantly produced, stable, and were efficiently secreted by bacteria in vitro. Moreover, these bacteria could all maintain functionally competent needle structures and controlled Yops secretion in vitro. In the presence of host cells however, bacteria producing the most genetically altered hybrids (+1 frameshift after 278 codon) had diminished control of polarized Yop translocation. This corresponded to significant attenuation in competitive survival assays in orally infected mice, although not at all to the same extent as Yersinia lacking both YopN and TyeA proteins. Based on these studies with engineered polypeptides, most likely a naturally occurring YopN-TyeA hybrid protein has the potential to influence T3S control and activity when produced during Yersinia-host cell contact.

  • 14.
    Andersson, Agneta
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå marina forskningscentrum (UMF).
    Jurgensone, Iveta
    Rowe, Owen F.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Simonelli, Paolo
    Bignert, Anders
    Lundberg, Erik
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå marina forskningscentrum (UMF).
    Karlsson, Jan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Can Humic Water Discharge Counteract Eutrophication in Coastal Waters?2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 4, s. e61293-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A common and established view is that increased inputs of nutrients to the sea, for example via river flooding, will cause eutrophication and phytoplankton blooms in coastal areas. We here show that this concept may be questioned in certain scenarios. Climate change has been predicted to cause increased inflow of freshwater to coastal areas in northern Europe. River waters in these areas are often brown from the presence of high concentrations of allochthonous dissolved organic carbon ( humic carbon), in addition to nitrogen and phosphorus. In this study we investigated whether increased inputs of humic carbon can change the structure and production of the pelagic food web in the recipient seawater. In a mesocosm experiment unfiltered seawater from the northern Baltic Sea was fertilized with inorganic nutrients and humic carbon (CNP), and only with inorganic nutrients (NP). The system responded differently to the humic carbon addition. In NP treatments bacterial, phytoplankton and zooplankton production increased and the systems turned net autotrophic, whereas the CNP-treatment only bacterial and zooplankton production increased driving the system to net heterotrophy. The size-structure of the food web showed large variations in the different treatments. In the enriched NP treatments the phytoplankton community was dominated by filamentous >20 mu m algae, while in the CNP treatments the phytoplankton was dominated by picocyanobacteria <5 mu m. Our results suggest that climate change scenarios, resulting in increased humic-rich river inflow, may counteract eutrophication in coastal waters, leading to a promotion of the microbial food web and other heterotrophic organisms, driving the recipient coastal waters to net-heterotrophy.

  • 15.
    Andersson, Gerhard
    et al.
    Department of Behavioural Sciences and Learning, Swedish Institute for Disability Research, Linköping University, Linkö ping, Sweden and Department of Clinical Neuroscience, Psychiatry Section, Karolinska Institutet, Stockholm, Sweden.
    Carlbring, Per
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Furmark, Tomas
    Department of Psychology, Uppsala University, Uppsala, Sweden.
    Therapist experience and knowledge acquisition in internet-delivered CBT for social anxiety disorder: a randomized controlled trial2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 5, s. e37411-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Guided internet-delivered cognitive behavior therapy (ICBT) has been tested in several trials on social anxiety disorder (SAD) with moderate to large effects. The aims of this study were threefold. First, to compare the effects of ICBT including online discussion forum with a moderated online discussion forum only. Second, to investigate if knowledge about SAD increased following treatment and third to compare the effects of inexperienced versus experienced therapists on patient outcomes.

    Methods: A total of 204 participants with a primary diagnosis of SAD were included and randomized to either guided ICBT or the control condition. ICBT consisted of a 9-week treatment program which was guided by either psychology students at MSc level (n = 6) or by licensed psychologists with previous experience of ICBT (n = 7). A knowledge test dealing with social anxiety was administered before and after treatment. Measures of social anxiety and secondary outcomes dealing with general anxiety, depression, and quality of life were administered before and after treatment. In addition, a 1-year follow-up was conducted on the treated individuals.

    Results: Immediately following treatment, the ICBT group showed superior outcome on the Liebowitz Social Anxiety Scale self-report version with a between group posttreatment Hedges geffect size ofg = 0.75. In addition, significant differences on all the secondary outcomes were observed. Gains were well maintained one year later. Knowledge, as assessed by the knowledge test, increased following treatment with little gain in the control group. Therapist experience did not result in different outcomes, but experienced therapists logged in less frequently compared to the inexperienced therapists, suggesting that they needed less time to support patients.

    Discussion: We conclude that guided ICBT reduce symptoms of SAD, increase knowledge about SAD and that therapist experience does not make a difference apart from the finding that experienced therapist may require less time to guide patients.

    Trial Registration: UMIN.ac.jp UMIN000001383

  • 16.
    Andersson, Ida E
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Andersson, C David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Batsalova, Tsvetelina
    Medicinal Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm.
    Dzhambazov, Balik
    Medicinal Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm.
    Holmdahl, Rikard
    Medicinal Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm.
    Kihlberg, Jan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Linusson, Anna
    AstraZeneca R&D Mölndal, Mölndal.
    Design of glycopeptides used to investigate class II MHC binding and T-Cell responses associated with autoimmune arthritis2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 3, s. e17881-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The glycopeptide fragment CII259–273 from type II collagen (CII) binds to the murine Aq and human DR4 class II Major Histocompatibility Complex (MHC II) proteins, which are associated with development of murine collagen-induced arthritis (CIA) and rheumatoid arthritis (RA), respectively. It has been shown that CII259–273 can be used in therapeutic vaccination of CIA. This glycopeptide also elicits responses from T-cells obtained from RA patients, which indicates that it has an important role in RA as well. We now present a methodology for studies of (glyco)peptide-receptor interactions based on a combination of structure-based virtual screening, ligand-based statistical molecular design and biological evaluations. This methodology included the design of a CII259–273 glycopeptide library in which two anchor positions crucial for binding in pockets of Aq and DR4 were varied. Synthesis and biological evaluation of the designed glycopeptides provided novel structure-activity relationship (SAR) understanding of binding to Aq and DR4. Glycopeptides that retained high affinities for these MHC II proteins and induced strong responses in panels of T-cell hybridomas were also identified. An analysis of all the responses revealed groups of glycopeptides with different response patterns that are of high interest for vaccination studies in CIA. Moreover, the SAR understanding obtained in this study provides a platform for the design of second-generation glycopeptides with tuned MHC affinities and T-cell responses.

  • 17.
    Andersson, Johanna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Rosell, Michelle
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Kockum, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Lilja-Lund, Otto
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Soderstrom, Lars
    Laurell, Katarina
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap.
    Prevalence of idiopathic normal pressure hydrocephalus: A prospective, population-based study2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 5, artikel-id e0217705Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Idiopathic normal pressure hydrocephalus (iNPH) causing gait impairment, dementia and urinary incontinence among the elderly, is probably under-diagnosed and under-treated. Despite being known since the 1960s, there is still a lack of prospective, population-based studies on the prevalence of iNPH. Such studies are warranted to minimize selection bias and estimate the true prevalence of the disease.

    Methods: The prevalence of iNPH was determined in a randomly selected sample of residents, aged 65 years and older, in the Swedish county of Jämtland. Out of 1,000 individuals invited to participate, 673 (67.3%) completed a questionnaire with seven questions on iNPH symptoms. A subgroup, with and without self-reported symptoms, participated in clinical and radiological evaluations and were diagnosed according to international guidelines. Measurement of cerebrospinal fluid opening pressure was not performed as it was considered too invasive.

    Results: Those who reported at least two symptoms in the questionnaire (n = 117) and 51 randomly selected individuals with 0–1 symptom participated in further examinations. Out of them, 25 individuals received the diagnosis probable iNPH according to American-European guidelines (except for the criterion of CSF opening pressure) corresponding to a prevalence of 3.7%. The prevalence of iNPH was four times higher among those aged 80 years and older (8.9%) than among those aged 65–79 years (2.1%) (p <0.001). The difference in prevalence between men (4.6%) and women (2.9%) was not significant (p = 0.24). When iNPH was diagnosed according to the Japanese guidelines the prevalence was 1.5%

    Conclusions: In this prospective, population-based study the prevalence of iNPH was 3.7% among individuals 65 years and older, and more common in the higher age group, 80 years and above. INPH should be increasingly recognized since it is a fairly common condition and an important cause of gait impairment and dementia among the elderly that can be effectively treated by shunt surgery.

  • 18. Andersson, Jon
    et al.
    Hjältén, Joakim
    Dynesius, Mats
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Wood-Inhabiting Beetles in Low Stumps, High Stumps and Logs on Boreal Clear-Cuts: Implications for Dead Wood Management2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 3, artikel-id e0118896Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The increasing demand for biofuels from logging residues require serious attention on the importance of dead wood substrates on clear-cuts for the many forestry-intolerant saproxylic (wood-inhabiting) species. In particular, the emerging harvest of low stumps motivates further study of these substrates. On ten clear-cuts we compared the species richness, abundance and species composition of saproxylic beetles hatching from four to nine year old low stumps, high stumps and logs of Norway spruce. By using emergence traps we collected a total of 2,670 saproxylic beetles among 195 species during the summers of 2006, 2007 and 2009. We found that the species assemblages differed significantly between high stumps and logs all three years. The species assemblages of low stumps, on the other hand, were intermediate to those found in logs and high stumps. There were also significant difference in species richness between the three examined years, and we found significant effect of substrate type on richness of predators and fungivores. As shown in previous studies of low stumps on clear-cuts they can sustain large numbers of different saproxylic beetles, including red-listed species. Our study does, in addition to this fact, highlight a possible problem in creating just one type of substrate as a tool for conservation in forestry. Species assemblages in high stumps did not differ significantly from those found in low stumps. Instead logs, which constitute a scarcer substrate type on clear-cuts, provided habitat for a more distinct assemblage of saproxylic species than high stumps. It can therefore be questioned whether high stumps are an optimal tool for nature conservation in clear-cutting forestry. Our results also indicate that low stumps constitute an equally important substrate as high stumps and logs, and we therefore suggest that stump harvesting is done after carefully evaluating measures to provide habitat for saproxylic organisms.

  • 19. Andersson, Karin
    et al.
    Pokrzywa, M
    Dacklin, Ingrid
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Lundgren, Erik
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Inhibition of TTR aggregation-induced cell death: a new role for serum amyloid P component2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Serum amyloid P component (SAP) is a glycoprotein that is universally found associated with different types of amyloid deposits. It has been suggested that it stabilizes amyloid fibrils and therefore protects them from proteolytic degradation.

    METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we show that SAP binds not only to mature amyloid fibrils but also to early aggregates of amyloidogenic mutants of the plasma protein transthyretin (TTR). It does not inhibit fibril formation of TTR mutants, which spontaneously form amyloid in vitro at physiological pH. We found that SAP prevents cell death induced by mutant TTR, while several other molecules that are also known to decorate amyloid fibrils do not have such effect. Using a Drosophila model for TTR-associated amyloidosis, we found a new role for SAP as a protective factor in inhibition of TTR-induced toxicity. Overexpression of mutated TTR leads to a neurological phenotype with changes in wing posture. SAP-transgenic flies were crossed with mutated TTR-expressing flies and the results clearly confirmed a protective effect of SAP on TTR-induced phenotype, with an almost complete reduction in abnormal wing posture. Furthermore, we found in vivo that binding of SAP to mutated TTR counteracts the otherwise detrimental effects of aggregation of amyloidogenic TTR on retinal structure.

    CONCLUSIONS/SIGNIFICANCE: Together, these two approaches firmly establish the protective effect of SAP on TTR-induced cell death and degenerative phenotypes, and suggest a novel role for SAP through which the toxicity of early amyloidogenic aggregates is attenuated.

  • 20. Ankarfeldt, Mikkel Z.
    et al.
    Ängquist, Lars
    Stocks, Tanja
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi. Department of Clinical Sciences in Malmö, Diabetes and Cardiovascular Diseases, Genetic Epidemiology, Lund University, Lund, Sweden.
    Jakobsen, Marianne U.
    Overvad, Kim
    Halkjær, Jytte
    Saris, Wim H. M.
    Astrup, Arne
    Sørensen, Thorkild I. A.
    Body characteristics, dietary protein and body weight regulation. Reconciling conflicting results from intervention and observational studies?2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 7, s. e101134-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Objectives: Physiological evidence indicates that high-protein diets reduce caloric intake and increase thermogenic response, which may prevent weight gain and regain after weight loss. Clinical trials have shown such effects, whereas observational cohort studies suggest an association between greater protein intake and weight gain. In both types of studies the results are based on average weight changes, and show considerable diversity in both directions. This study investigates whether the discrepancy in the evidence could be due to recruitment of overweight and obese individuals into clinical trials. Subjects/Methods: Data were available from the European Diet, Obesity and Genes (DiOGenes) post-weight-loss weight-maintenance trial and the Danish Diet, Cancer and Health (DCH) cohort. Participants of the DCH cohort were matched with participants from the DiOGenes trial on gender, diet, and body characteristics. Different subsets of the DCH-participants, comparable with the trial participants, were analyzed for weight maintenance according to the randomization status (high or low protein) of the matched trial participants. Results: Trial participants were generally heavier, had larger waist circumference and larger fat mass than the participants in the entire DCH cohort. A better weight maintenance in the high-protein group compared to the low protein group was observed in the subgroups of the DCH cohort matching body characteristics of the trial participants. Conclusion: This modified observational study, minimized the differences between the RCT and observational data with regard to dietary intake, participant characteristics and statistical analysis. Compared with low protein diet the high protein diet was associated with better weight maintenance when individuals with greater body mass index and waist circumference were analyzed. Selecting subsets of large-scale observational cohort studies with similar characteristics as participants in clinical trials may reconcile the otherwise conflicting results.

  • 21. Annandale, Ellen
    et al.
    Hammarström, Anne
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Socialmedicin.
    Gender Inequality in the Couple Relationship and Leisure-Based Physical Exercise2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 7, artikel-id e0133348Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: To analyse whether gender inequality in the couple relationship was related to leisure-based physical activity, after controlling for earlier physical activity and confounders. Methods: Data drawn from the Northern Swedish Cohort of all pupils in their final year of compulsory schooling in a town in the North of Sweden. The sample consisted of 772 respondents (n = 381 men, n = 391 women) in the 26-year follow-up (in 2007, aged 42) who were either married or cohabiting. Ordinal regression, for men and women separately, was used to assess the association between gender inequality (measured as self-perceived equality in the couple relationship using dummy variables) and a measure of exercise frequency, controlling for prior exercise frequency, socioeconomic status, the presence of children in the home, and longer than usual hours in paid work. Results: The perception of greater gender equality in the couple relationship was associated with higher levels of physical activity for both men and women. This remained significant when the other variables were controlled for. Amongst men the confidence intervals were high. Conclusions: The results point to the potential of perceived gender equality in the couple relationship to counteract the general time poverty and household burden that often arises from the combination of paid work and responsibility for children and the home, especially for women. The high confidence intervals among men indicate the need for more research within the field with larger samples.

  • 22.
    Antoniewicz, Lukasz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Karolinska Institutet, Department of Clinical Sciences, Division of Internal Medicine, Danderyd Hospital, Stockholm, Sweden.
    Novo, Mirza
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Bosson, Jenny A.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Lundbäck, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Brief exposure to Swedish snus causes divergent vascular responses in healthy male and female volunteers2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 4, artikel-id e0195493Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: The use of Swedish oral moist snuff, known as snus, has for a long time been limited to the Scandinavian countries. With declining cigarette sales in the western world, tobacco companies have looked to the development of alternative tobacco products. In 2006 snus products were launched in the US. Even though several studies have demonstrated negative health effects, snus is often depicted as harmless.

    The aim of the present study was to investigate acute vascular effects of snus as measured by arterial stiffness as well as blood pressure and heart rate.

    Methods: Two separate randomized double-blind crossover studies with the same study design were pooled for analysis. Twenty-nine healthy snus-users (17 females, 12 males) were included. Snus (Göteborgs Rapé) and tobacco free snus (Onico) were administered in a randomized order at two separate visits. Arterial stiffness, blood pressure and heart rate were measured at baseline as well as every five minutes for 40 minutes during exposure. Following snus removal, measurements continued for 30 minutes post exposure. Arterial stiffness was measured using pulse wave velocity (Vicorder) and pulse wave analysis (Sphygmocor).

    Results: Compared to placebo, snus significantly increased systolic and diastolic blood pressure as well as heart rate, however, only in females (p = 0.004, p = 0.006 and p<0.001 respectively). No changes were seen in arterial stiffness measurements in either gender.

    Conclusion: We observed an increase in blood pressure and heart rate only in females, but not in males due to snus usage as compared to placebo. This novel finding was surprising and needs to be further investigated considering most of the earlier studies have mainly focused on male snus users and the increasing usage of snus among females.

  • 23.
    Antti, Henrik
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Fahlgren, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Näsström, Elin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Kouremenos, Konstantinos
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Sundén-Cullberg, Jonas
    Guo, Yongzhi
    Moritz, Thomas
    Wolf-Watz, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Infektionssjukdomar.
    Fällman, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Metabolic profiling for detection of staphylococcus aureus infection and antibiotic resistance2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 2, artikel-id e56971Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Due to slow diagnostics, physicians must optimize antibiotic therapies based on clinical evaluation of patients without specific information on causative bacteria. We have investigated metabolomic analysis of blood for the detection of acute bacterial infection and early differentiation between ineffective and effective antibiotic treatment. A vital and timely therapeutic difficulty was thereby addressed: the ability to rapidly detect treatment failures because of antibiotic-resistant bacteria. Methicillin-resistant (MRSA) and methicillin-sensitive (MSSA) were used and for infecting mice, while natural MSSA infection was studied in humans. Samples of bacterial growth media, the blood of infected mice and of humans were analyzed with combined Gas Chromatography/Mass Spectrometry. Multivariate data analysis was used to reveal the metabolic profiles of infection and the responses to different antibiotic treatments. experiments resulted in the detection of 256 putative metabolites and mice infection experiments resulted in the detection of 474 putative metabolites. Importantly, ineffective and effective antibiotic treatments were differentiated already two hours after treatment start in both experimental systems. That is, the ineffective treatment of MRSA using cloxacillin and untreated controls produced one metabolic profile while all effective treatment combinations using cloxacillin or vancomycin for MSSA or MRSA produced another profile. For further evaluation of the concept, blood samples of humans admitted to intensive care with severe sepsis were analyzed. One hundred thirty-three putative metabolites differentiated severe MSSA sepsis (n = 6) from severe sepsis (n = 10) and identified treatment responses over time. Combined analysis of human, , and mice samples identified 25 metabolites indicative of effective treatment of sepsis. Taken together, this study provides a proof of concept of the utility of analyzing metabolite patterns in blood for early differentiation between ineffective and effective antibiotic treatment in acute infections.

  • 24.
    Antti, Henrik
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Sellstedt, Magnus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Metabolic effects of an aspartate aminotransferase-inhibitor on two T-cell lines2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 12, artikel-id e0208025Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An emerging method to help elucidate the mode of action of experimental drugs is to use untargeted metabolomics of cell-systems. The interpretations of such screens are however complex and more examples with inhibitors of known targets are needed. Here two T-cell lines were treated with an inhibitor of aspartate aminotransferase and analyzed with untargeted GC-MS. The interpretation of the data was enhanced by the use of two different cell-lines and supports aspartate aminotransferase as a target. In addition, the data suggest an unexpected off-target effect on glutamate decarboxylase. The results exemplify the potency of metabolomics to provide insight into both mode of action and off-target effects of drug candidates.

  • 25.
    Arvidsson, Sandra
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Pilebro, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Westermark, Per
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Amyloid Cardiomyopathy in Hereditary Transthyretin V30M Amyloidosis - Impact of Sex and Amyloid Fibril Composition2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 11, artikel-id e0143456Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Transthyretin V30M (ATTR V30M) amyloidosis is a phenotypically diverse disease with symptoms ranging from predominant neuropathy to exclusive cardiac manifestations. The aims of this study were to determine the dispersion of the two types of fibrils found in Swedish ATTR V30M patients -Type A consisting of a mixture of truncated and full length ATTR fibrils and type B fibrils consisting of full length fibrils, and to estimate the severity of cardiac dysfunction in relation to fibril composition and sex.

    MATERIAL AND METHODS: Echocardiographic data were analysed in 107 Swedish ATTR V30M patients with their fibril composition determined as either type A or type B. Measurements of left ventricular (LV) dimensions and evaluation of systolic and diastolic function including speckle tracking derived strain were performed. Patients were grouped according to fibril type and sex. Multivariate linear regression was utilised to determine factors of significant impact on LV thickness.

    RESULTS: There was no significant difference in proportions of the two types of fibrils between men and women. In patients with type A fibrils, women had significantly lower median septal (p = 0.007) and posterior wall thicknesses (p = 0.010), lower median LV mass indexed to height (p = 0.008), and higher septal strain (p = 0.037), as compared to males. These differences were not apparent in patients with type B fibrils. Multiple linear regression analysis revealed that fibril type, sex and age all had significant impact on LV septal thickness.

    CONCLUSION: This study demonstrates a clear difference between sexes in the severity of amyloid heart disease in ATTR V30M amyloidosis patients. Even though type A fibrils were associated with more advanced amyloid heart disease compared to type B, women with type A fibrils generally developed less cardiac infiltration than men. The differences may explain the better outcome for liver transplanted late-onset female patients compared to males.

  • 26. Asghar, Naveed
    et al.
    Lindblom, Pontus
    Melik, Wessam
    Lindqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Haglund, Mats
    Forsberg, Pia
    Överby, Anna K.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Andreassen, Åshild
    Lindgren, Per-Eric
    Johansson, Magnus
    Tick-borne encephalitis virus sequenced directly from questing and blood-feeding ticks reveals quasispecies variance2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 7, s. e103264-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The increased distribution of the tick-borne encephalitis virus (TBEV) in Scandinavia highlights the importance of characterizing novel sequences within the natural foci. In this study, two TBEV strains: the Norwegian Mandal 2009 (questing nymphs pool) and the Swedish Saringe 2009 (blood-fed nymph) were sequenced and phylogenetically characterized. Interestingly, the sequence of Mandal 2009 revealed the shorter form of the TBEV genome, similar to the highly virulent Hypr strain, within the 3' non-coding region (3'NCR). A different genomic structure was found in the 3'NCR of Saringe 2009, as in-depth analysis demonstrated TBEV variants with different lengths within the poly(A) tract. This shows that TBEV quasispecies exists in nature and indicates a putative shift in the quasispecies pool when the virus switches between invertebrate and vertebrate environments. This prompted us to further sequence and analyze the 3'NCRs of additional Scandinavian TBEV strains and control strains, Hypr and Neudoerfl. Toro 2003 and Habo 2011 contained mainly a short (A) 3C(A)6 poly(A) tract. A similar pattern was observed for the human TBEV isolates 1993/783 and 1991/4944; however, one clone of 1991/4944 contained an (A) 3C(A)11 poly(A) sequence, demonstrating that quasispecies with longer poly(A) could be present in human isolates. Neudoerfl has previously been reported to contain a poly(A) region, but to our surprise the resequenced genome contained two major quasispecies variants, both lacking the poly(A) tract. We speculate that the observed differences are important factors for the understanding of virulence, spread, and control of the TBEV.

  • 27. Atherton, Sarah
    et al.
    Jondelius, Ulf
    A taxonomic review and revisions of Microstomidae (Platyhelminthes: Macrostomorpha)2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 4, artikel-id e0212073Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Microstomidae (Platyhelminthes: Macrostomorpha) diversity has been almost entirely ignored within recent years, likely due to inconsistent and often old taxonomic literature and a general rarity of sexually mature collected specimens. Herein, we reconstruct the phylogenetic relationships of the group using both previously published and new 18S and CO1 gene sequences. We present some taxonomic revisions of Microstomidae and further describe 8 new species of Microstomum based on both molecular and morphological evidence. Finally, we briefly review the morphological taxonomy of each species and provide a key to aid in future research and identification that is not dependent on reproductive morphology. Our goal is to clarify the taxonomy and facilitate future research into an otherwise very understudied group of tiny (but important) flatworms.

  • 28. Audet, Carolyn M.
    et al.
    Ngobeni, Sizzy
    Graves, Erin
    Wagner, Ryan G.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. MRC/Wits Agincourt Research Unit, School of Public Health, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa.
    Mixed methods inquiry into traditional healers' treatment of mental, neurological and substance abuse disorders in rural South Africa2017Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, nr 12, artikel-id e0188433Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Traditional healers are acceptable and highly accessible health practitioners throughout sub-Saharan Africa. Patients in South Africa often seek concurrent traditional and allopathic treatment leading to medical pluralism. Methods & findings: We studied the cause of five traditional illnesses known locally as "Mavabyi ya nhloko" (sickness of the head), by conducting 27 in-depth interviews and 133 surveys with a randomly selected sample of traditional healers living and working in rural, northeastern South Africa. These interviews were carried out to identify treatment practices of mental, neurological, and substance abuse (MNS) disorders. Participating healers were primarily female (77%), older in age (median: 58.0 years; interquartile range [IQR]: 50-67), had very little formal education (median: 3.7 years; IQR: 3.2-4.2), and had practiced traditional medicine for many years (median: 17 years; IQR: 9.5-30). Healers reported having the ability to successfully treat: seizure disorders (47%), patients who have lost touch with reality (47%), paralysis on one side of the body (59%), and substance abuse (21%). Female healers reported a lower odds of treating seizure disorders (Odds Ratio (OR): 0.47), patients who had lost touch with reality (OR: 0.26; p-value<0.05), paralysis of one side of the body (OR: 0.36), and substance abuse (OR: 0.36) versus males. Each additional year of education received was found to be associated with lower odds, ranging from 0.13-0.27, of treating these symptoms. Each additional patient seen by healers in the past week was associated with roughly 1.10 higher odds of treating seizure disorders, patients who have lost touch with reality, paralysis of one side of the body, and substance abuse. Healers charged a median of 500 South African Rand (similar to US$35) to treat substance abuse, 1000 Rand (similar to US$70) for seizure disorders or paralysis of one side of the body, and 1500 Rand (similar to US$105) for patients who have lost touch with reality. Conclusions: While not all healers elect to treat MNS disorders, many continue to do so, delaying allopathic health services to acutely ill patients.

  • 29.
    Backman, Ludvig
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Fong, Gloria
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Andersson, Gustav
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Scott, Alexander
    Vancouver Coastal Health and Research Institute, University of British Columbia, Vancouver.
    Danielson, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Substance P is a mechanoresponsive, autocrine regulator of human tenocyte proliferation2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 11, s. e27209-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    It has been hypothesised that substance P (SP) may be produced by primary fibroblastic tendon cells (tenocytes), and that this production, together with the widespread distribution of the neurokinin-1 receptor (NK-1 R) in tendon tissue, could play an important role in the development of tendinopathy, a condition of chronic tendon pain and thickening. The aim of this study was to examine the possibility of endogenous SP production and the expression of NK-1 R by human tenocytes. Because tendinopathy is related to overload, and because the predominant tissue pathology (tendinosis) underlying early tendinopathy is characterized by tenocyte hypercellularity, the production of SP in response to loading/strain and the effects of exogenously administered SP on tenocyte proliferation were also studied. A cell culture model of primary human tendon cells was used. The vast majority of tendon cells were immunopositive for the tenocyte/fibroblast markers tenomodulin and vimentin, and immunocytochemical counterstaining revealed that positive immunoreactions for SP and NK-1 R were seen in a majority of these cells. Gene expression analyses showed that mechanical loading (strain) of tendon cell cultures using the FlexCell (R) technique significantly increased the mRNA levels of SP, whereas the expression of NK-1 R mRNA decreased in loaded as compared to unloaded tendon cells. Reduced NK-1 R protein was also observed, using Western blot, after exogenously administered SP at a concentration of 10(-7) M. SP exposure furthermore resulted in increased cell metabolism, increased cell viability, and increased cell proliferation, all of which were found to be specifically mediated via the NK-1 R; this in turn involving a common mitogenic cell signalling pathway, namely phosphorylation of ERK1/2. This study indicates that SP, produced by tenocytes in response to mechanical loading, may regulate proliferation through an autocrine loop involving the NK-1 R.

  • 30.
    Baek, Seung Ki
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Choi, Jung-Kyoo
    Kim, Beom Jun
    Dworkin's Paradox2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 6, s. e38529-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    How to distribute welfare in a society is a key issue in the subject of distributional justice, which is deeply involved with notions of fairness. Following a thought experiment by Dworkin, this work considers a society of individuals with different preferences on the welfare distribution and an official to mediate the coordination among them. Based on a simple assumption that an individual's welfare is proportional to how her preference is fulfilled by the actual distribution, we show that an egalitarian preference is a strict Nash equilibrium and can be favorable even in certain inhomogeneous situations. These suggest how communication can encourage and secure a notion of fairness.

  • 31. Bahnan, Wael
    et al.
    Boettner, Douglas R.
    Westermark, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Fällman, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Schesser, Kurt
    Pathogenic Yersinia Promotes Its Survival by Creating an Acidic Fluid-Accessible Compartment on the Macrophage Surface2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 8, artikel-id e0133298Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Microbial pathogens and host immune cells each initiate events following their interaction in an attempt to drive the outcome to their respective advantage. Here we show that the bacterial pathogen Yersinia pseudotuberculosis sustains itself on the surface of a macrophage by forming acidic fluid-accessible compartments that are partially bounded by the host cell plasma membrane. These Yersinia-containing acidic compartments (YACs) are bereft of the early endosomal marker EEA1 and the lysosomal antigen LAMP1 and readily form on primary macrophages as well as macrophage-like cell lines. YAC formation requires the presence of the Yersinia virulence plasmid which encodes a type III secretion system. Unexpectedly, we found that the initial formation of YACs did not require translocation of the type III effectors into the host cell cytosol; however, the duration of YACs was markedly greater in infections using translocation-competent Y. pseudotuberculosis strains as well as strains expressing the effector YopJ. Furthermore, it was in this translocation- and YopJ-dependent phase of infection that the acidic environment was critical for Y. pseudotuberculosis survival during its interaction with macrophages. Our findings indicate that during its extracellular phase of infection Y. pseudotuberculosis initiates and then, by a separate mechanism, stabilizes the formation of a highly intricate structure on the surface of the macrophage that is disengaged from the endocytic pathway.

  • 32.
    Bandau, Franziska
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Decker, Vicki Huizu Guo
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Gundale, Michael J.
    Department of Forest Ecology and Management, Swedish University of Agricultural Sciences, SE 90183 Umeå, Sweden.
    Albrectsen, Benedicte Riber
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Department of Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, DK 1871 Frederiksberg C, Denmark.
    Genotypic tannin levels in Populus tremula impact the way nitrogen enrichment affects growth and allocation responses for some traits and not for others2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 10, artikel-id e0140971Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Plant intraspecific variability has been proposed as a key mechanism by which plants adapt to environmental change. In boreal forests where nitrogen availability is strongly limited, nitrogen addition happens indirectly through atmospheric N deposition and directly through industrial forest fertilization. These anthropogenic inputs of N have numerous environmental consequences, including shifts in plant species composition and reductions in plant species diversity. However, we know less about how genetic differences within plant populations determine how species respond to eutrophication in boreal forests. According to plant defense theories, nitrogen addition will cause plants to shift carbon allocation more towards growth and less to chemical defense, potentially enhancing vulnerability to antagonists. Aspens are keystone species in boreal forests that produce condensed tannins to serve as chemical defense. We conducted an experiment using ten Populus tremula genotypes from the Swedish Aspen Collection that express extreme levels of baseline investment into foliar condensed tannins. We investigated whether investment into growth and phenolic defense compounds in young plants varied in response to two nitrogen addition levels, corresponding to atmospheric N deposition and industrial forest fertilization. Nitrogen addition generally caused growth to increase, and tannin levels to decrease; however, individualistic responses among genotypes were found for height growth, biomass of specific tissues, root: shoot ratios, and tissue lignin and N concentrations. A genotype's baseline ability to produce and store condensed tannins also influenced plant responses to N, although this effect was relatively minor. High-tannin genotypes tended to grow less biomass under low nitrogen levels and more at the highest fertilization level. Thus, the ability in aspen to produce foliar tannins is likely associated with a steeper reaction norm of growth responses, which suggests a higher plasticity to nitrogen addition, and potentially an advantage when adapting to higher concentrations of soil nitrogen.

  • 33.
    Barajas-Lopez, Juan de Dios
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Kremnev, Dmitry
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Shaikhali, Jehad
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Pinas-Fernandez, Aurora
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Strand, Åsa
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    PAPP5 is involved in the tetrapyrrole mediated plastid signalling during chloroplast development2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 3, artikel-id e60305Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The initiation of chloroplast development in the light is dependent on nuclear encoded components. The nuclear genes encoding key components in the photosynthetic machinery are regulated by signals originating in the plastids. These plastid signals play an essential role in the regulation of photosynthesis associated nuclear genes (PhANGs) when proplastids develop into chloroplasts. One of the plastid signals is linked to the tetrapyrrole biosynthesis and accumulation of the intermediates the Mg-ProtoIX and its methyl ester Mg-ProtoIX-ME. Phytochrome-Associated Protein Phosphatase 5 (PAPP5) was isolated in a previous study as a putative Mg-ProtoIX interacting protein. In order to elucidate if there is a biological link between PAPP5 and the tetrapyrrole mediated signal we generated double mutants between the Arabidopsis papp5 and the crd mutants. The crd mutant over-accumulates Mg-ProtoIX and Mg-ProtoIX-ME and the tetrapyrrole accumulation triggers retrograde signalling. The crd mutant exhibits repression of PhANG expression, altered chloroplast morphology and a pale phenotype. However, in the papp5crd double mutant, the crd phenotype is restored and papp5crd accumulated wild type levels of chlorophyll, developed proper chloroplasts and showed normal induction of PhANG expression in response to light. Tetrapyrrole feeding experiments showed that PAPP5 is required to respond correctly to accumulation of tetrapyrroles in the cell and that PAPP5 is most likely a component in the plastid signalling pathway down stream of the tetrapyrrole Mg-ProtoIX/Mg-ProtoIX-ME. Inhibition of phosphatase activity phenocopied the papp5crd phenotype in the crd single mutant demonstrating that PAPP5 phosphatase activity is essential to mediate the retrograde signal and to suppress PhANG expression in the crd mutant. Thus, our results suggest that PAPP5 receives an inbalance in the tetrapyrrole biosynthesis through the accumulation of Mg-ProtoIX and acts as a negative regulator of PhANG expression during chloroplast biogenesis and development.

  • 34.
    Barcena-Uribarri, Ivan
    et al.
    Universität Würzburg, Germany.
    Thein, Marcus
    Universität Würzburg and Jacobs University Bremen, Germany.
    Maier, Elke
    Universität Würzburg, Germany.
    Bonde, Mari
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Bergström, Sven
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Benz, Roland
    Universität Würzburg, Germany.
    Use of Nonelectrolytes Reveals the Channel Size and Oligomeric Constitution of the Borrelia burgdorferi P66 Porin2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 11, s. e78272-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the Lyme disease spirochete Borrelia burgdorferi, the outer membrane protein P66 is capable of pore formation with an atypical high single-channel conductance of 11 nS in 1 M KCl, which suggested that it could have a larger diameter than 'normal' Gram-negative bacterial porins. We studied the diameter of the P66 channel by analyzing its single-channel conductance in black lipid bilayers in the presence of different nonelectrolytes with known hydrodynamic radii. We calculated the filling of the channel with these nonelectrolytes and the results suggested that nonelectrolytes (NEs) with hydrodynamic radii of 0.34 nm or smaller pass through the pore, whereas neutral molecules with greater radii only partially filled the channel or were not able to enter it at all. The diameter of the entrance of the P66 channel was determined to be <= 1.9 nm and the channel has a central constriction of about 0.8 nm. The size of the channel appeared to be symmetrical as judged from one-sidedness of addition of NEs. Furthermore, the P66-induced membrane conductance could be blocked by 80-90% by the addition of the nonelectrolytes PEG 400, PEG 600 and maltohexaose to the aqueous phase in the low millimolar range. The analysis of the power density spectra of ion current through P66 after blockage with these NEs revealed no chemical reaction responsible for channel block. Interestingly, the blockage of the single-channel conductance of P66 by these NEs occurred in about eight subconductance states, indicating that the P66 channel could be an oligomer of about eight individual channels. The organization of P66 as a possible octamer was confirmed by Blue Native PAGE and immunoblot analysis, which both demonstrated that P66 forms a complex with a mass of approximately 460 kDa. Two dimension SDS PAGE revealed that P66 is the only polypeptide in the complex.

  • 35. Barman, Malin
    et al.
    Johansson, Sara
    Hesselmar, Bill
    Wold, Agnes E.
    Sandberg, Ann-Sofie
    Sandin, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    High Levels of Both n-3 and n-6 Long-Chain Polyunsaturated Fatty Acids in Cord Serum Phospholipids Predict Allergy Development2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 7, s. e67920-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Long-chain polyunsaturated fatty acids (LCPUFAs) reduce T-cell activation and dampen inflammation. They might thereby counteract the neonatal immune activation and hamper normal tolerance development to harmless environmental antigens. We investigated whether fatty acid composition of cord serum phospholipids affects allergy development up to age 13 years. Methods: From a population-based birth-cohort born in 1996/7 and followed until 13 years of age (n = 794), we selected cases with atopic eczema (n = 37) or respiratory allergy (n = 44), as well as non-allergic non-sensitized controls (n = 48) based on diagnosis at 13 years of age. Cord and maternal sera obtained at delivery from cases and controls were analysed for proportions of saturated, monounsaturated and polyunsaturated fatty acids among serum phospholipids. Results: The cord serum phospholipids from subject who later developed either respiratory allergy or atopic eczema had significantly higher proportions of 5/8 LCPUFA species, as well as total n-3 LCPUFA, total n-6 LCPUFA and total LCPUFA compared to cord serum phospholipids from controls who did not develop allergy (P < 0.001 for all comparisons). Conversely, individuals later developing allergy had lower proportion of the monounsaturated fatty acid 18:1n-9 as well as total MUFA (p < 0.001) among cord serum phospholipids. The risk of respiratory allergy at age 13 increased linearly with the proportion of n-3 LCPUFA (P-trend < 0.001), n-6 LCPUFA (P-trend = 0.001), and total LCPUFA (P-trend < 0.001) and decreased linearly with the proportions of total MUFA (P-trend = 0.025) in cord serum phospholipids. Furthermore, Kaplan-Meier estimates of allergy development demonstrated that total LCPUFA proportion in cord serum phospholipids was significantly associated with respiratory allergy (P = 0.008) and sensitization (P = 0.002), after control for sex and parental allergy. Conclusion: A high proportion of long-chain PUFAs among cord serum phospholipids may predispose to allergy development. The mechanism is unknown, but may involve dampening of the physiologic immune activation in infancy needed for proper maturation of the infant's immune system.

  • 36. Barrenas, Fredrik
    et al.
    Chavali, Sreenivas
    Holme, Petter
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Mobini, Reza
    Benson, Mikael
    Network properties of complex human disease genes identified through genome-wide association studies2009Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, nr 11, s. e8090-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Previous studies of network properties of human disease genes have mainly focused on monogenic diseases or cancers and have suffered from discovery bias. Here we investigated the network properties of complex disease genes identified by genome-wide association studies (GWAs), thereby eliminating discovery bias.

    Principal findings We derived a network of complex diseases (n = 54) and complex disease genes (n = 349) to explore the shared genetic architecture of complex diseases. We evaluated the centrality measures of complex disease genes in comparison with essential and monogenic disease genes in the human interactome. The complex disease network showed that diseases belonging to the same disease class do not always share common disease genes. A possible explanation could be that the variants with higher minor allele frequency and larger effect size identified using GWAs constitute disjoint parts of the allelic spectra of similar complex diseases. The complex disease gene network showed high modularity with the size of the largest component being smaller than expected from a randomized null-model. This is consistent with limited sharing of genes between diseases. Complex disease genes are less central than the essential and monogenic disease genes in the human interactome. Genes associated with the same disease, compared to genes associated with different diseases, more often tend to share a protein-protein interaction and a Gene Ontology Biological Process.

    Conclusions This indicates that network neighbors of known disease genes form an important class of candidates for identifying novel genes for the same disease.

  • 37.
    Bartels, Pia
    et al.
    Department of Ecology and Genetics, Limnology, Uppsala University, Uppsala, Sweden.
    Hirsch, Philipp E.
    Svanbäck, Richard
    Eklöv, Peter
    Water Transparency Drives Intra-Population Divergence in Eurasian Perch (Perca fluviatilis)2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 8, s. e43641-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Trait combinations that lead to a higher efficiency in resource utilization are important drivers of divergent natural selection and adaptive radiation. However, variation in environmental features might constrain foraging in complex ways and therefore impede the exploitation of critical resources. We tested the effect of water transparency on intra-population divergence in morphology of Eurasian perch (Perca fluviatilis) across seven lakes in central Sweden. Morphological divergence between near-shore littoral and open-water pelagic perch substantially increased with increasing water transparency. Reliance on littoral resources increased strongly with increasing water transparency in littoral populations, whereas littoral reliance was not affected by water transparency in pelagic populations. Despite the similar reliance on pelagic resources in pelagic populations along the water transparency gradient, the utilization of particular pelagic prey items differed with variation in water transparency in pelagic populations. Pelagic perch utilized cladocerans in lakes with high water transparency and copepods in lakes with low water transparency. We suggest that under impaired visual conditions low utilization of littoral resources by littoral perch and utilization of evasive copepods by pelagic perch may lead to changes in morphology. Our findings indicate that visual conditions can affect population divergence in predator populations through their effects on resource utilization.

  • 38. Bawah, Ayaga
    et al.
    Houle, Brian
    Alam, Nurul
    Razzaque, Abdur
    Streatfield, Peter Kim
    Debpuur, Cornelius
    Welaga, Paul
    Oduro, Abraham
    Hodgson, Abraham
    Tollman, Stephen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. MRC/Wits Rural Public Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa ; INDEPTH Network, Accra, Ghana.
    Collinson, Mark
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. MRC/Wits Rural Public Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa ; INDEPTH Network, Accra, Ghana.
    Kahn, Kathleen
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. MRC/Wits Rural Public Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa ; INDEPTH Network, Accra, Ghana.
    Toan, Tran Khan
    Phuc, Ho Dang
    Chuc, Nguyen Thi Kim
    Sankoh, Osman
    Clark, Samuel J.
    The Evolving Demographic and Health Transition in Four Low- and Middle-Income Countries: Evidence from Four Sites in the INDEPTH Network of Longitudinal Health and Demographic Surveillance Systems2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 6, artikel-id e0157281Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This paper contributes evidence documenting the continued decline in all-cause mortality and changes in the cause of death distribution over time in four developing country populations in Africa and Asia. We present levels and trends in age-specific mortality (all-cause and cause-specific) from four demographic surveillance sites: Agincourt (South Africa), Navrongo (Ghana) in Africa; Filabavi (Vietnam), Matlab (Bangladesh) in Asia. We model mortality using discrete time event history analysis. This study illustrates how data from INDEPTH Network centers can provide a comparative, longitudinal examination of mortality patterns and the epidemiological transition. Health care systems need to be reconfigured to deal simultaneously with continuing challenges of communicable disease and increasing incidence of non-communicable diseases that require long-term care. In populations with endemic HIV, long-term care of HIV patients on ART will add to the chronic care needs of the community.

  • 39. Bengtsson, Anders A.
    et al.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Wuttge, Dirk M.
    Sturfelt, Gunnar
    Theander, Elke
    Donten, Magdalena
    Moritz, Thomas
    Sennbro, Carl-Johan
    Torell, Frida
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lood, Christian
    Surowiec, Izabella
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Rännar, Stefan
    Lundstedt, Torbjörn
    Metabolic Profiling of Systemic Lupus Erythematosus and Comparison with Primary Sjögren’s Syndrome and Systemic Sclerosis2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 7, artikel-id e0159384Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease which can affect most organ systems including skin, joints and the kidney. Clinically, SLE is a heterogeneous disease and shares features of several other rheumatic diseases, in particular primary Sjögrens syndrome (pSS) and systemic sclerosis (SSc), why it is difficult to diag- nose The pathogenesis of SLE is not completely understood, partly due to the heterogeneity of the disease. This study demonstrates that metabolomics can be used as a tool for improved diagnosis of SLE compared to other similar autoimmune diseases. We observed differences in metabolic profiles with a classification specificity above 67% in the comparison of SLE with pSS, SSc and a matched group of healthy individuals. Selected metabolites were also significantly different between studied diseases. Biochemical pathway analysis was conducted to gain understanding of underlying pathways involved in the SLE pathogenesis. We found an increased oxidative activity in SLE, supported by increased xanthine oxidase activity and an increased turnover in the urea cycle. The most discriminatory metabolite observed was tryptophan, with decreased levels in SLE patients compared to control groups. Changes of tryptophan levels were related to changes in the activity of the aromatic amino acid decarboxylase (AADC) and/or to activation of the kynurenine pathway. 

  • 40. Bengtsson, Fredrik
    et al.
    Brasselet, Romain
    Johansson, Roland S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
    Arleo, Angelo
    Jörntell, Henrik
    Integration of sensory quanta in cuneate nucleus neurons in vivo2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 2, s. e56630-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Discriminative touch relies on afferent information carried to the central nervous system by action potentials (spikes) in ensembles of primary afferents bundled in peripheral nerves. These sensory quanta are first processed by the cuneate nucleus before the afferent information is transmitted to brain networks serving specific perceptual and sensorimotor functions. Here we report data on the integration of primary afferent synaptic inputs obtained with in vivo whole cell patch clamp recordings from the neurons of this nucleus. We find that the synaptic integration in individual cuneate neurons is dominated by 4-8 primary afferent inputs with large synaptic weights. In a simulation we show that the arrangement with a low number of primary afferent inputs can maximize transfer over the cuneate nucleus of information encoded in the spatiotemporal patterns of spikes generated when a human fingertip contact objects. Hence, the observed distributions of synaptic weights support high fidelity transfer of signals from ensembles of tactile afferents. Various anatomical estimates suggest that a cuneate neuron may receive hundreds of primary afferents rather than 4-8. Therefore, we discuss the possibility that adaptation of synaptic weight distribution, possibly involving silent synapses, may function to maximize information transfer in somatosensory pathways.

  • 41. Berg, Cecilia
    et al.
    Bäckström, Tobias
    Winberg, Svante
    Lindberg, Richard
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Brandt, Ingvar
    Developmental exposure to fluoxetine modulates the serotonin system in hypothalamus2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 1, artikel-id e55053Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLU, Prozac®) is commonly prescribed for depression in pregnant women. This results in SSRI exposure of the developing fetus. However, there are knowledge gaps regarding the impact of SSRI exposure during development. Given the role of serotonin in brain development and its cross-talk with sex hormone function, we investigated effects of developmental exposure to pharmacologically relevant concentrations of FLU (3 and 30 nM (measured)) on brain neurotransmitter levels, gonadal differentiation, aromatase activity in brain and gonads, and the thyroid system, using the Xenopus tropicalis model. Tadpoles were chronically exposed (8 weeks) until metamorphosis. At metamorphosis brains were cryosectioned and levels of serotonin, dopamine, norepinephrine, and their metabolites 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were measured in discrete regions (telencephalon, hypothalamus and the reticular formation) of the cryosections using high-performance liquid chromatography. Exposure to 30 nM FLU increased the concentration of 5-hydroxyindoleacetic acid in hypothalamus compared with controls. FLU exposure did not affect survival, time to metamorphosis, thyroid histology, gonadal sex differentiation, or aromatase activity implying that the effect on the serotonergic neurotransmitter system in the hypothalamus region was specific. The FLU concentration that impacted the serotonin system is lower than the concentration measured in umbilical cord serum, suggesting that the serotonin system of the developing brain is highly sensitive to in utero exposure to FLU. To our knowledge this is the first study showing effects of developmental FLU exposure on brain neurochemistry. Given that SSRIs are present in the aquatic environment the current results warrant further investigation into the neurobehavioral effects of SSRIs in aquatic wildlife.

  • 42. Berg, Kirsti
    et al.
    Ericsson, Madelene
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Lindgren, Mikael
    Gustafsson, Håkan
    A High Precision Method for Quantitative Measurements of Reactive Oxygen Species in Frozen Biopsies2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 3, s. e90964-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: An electron paramagnetic resonance (EPR) technique using the spin probe cyclic hydroxylamine 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH) was introduced as a versatile method for high precision quantification of reactive oxygen species, including the superoxide radical in frozen biological samples such as cell suspensions, blood or biopsies. Materials and Methods: Loss of measurement precision and accuracy due to variations in sample size and shape were minimized by assembling the sample in a well-defined volume. Measurement was carried out at low temperature (150 K) using a nitrogen flow Dewar. The signal intensity was measured from the EPR 1st derivative amplitude, and related to a sample, 3-carboxy-proxyl (CPN) with known spin concentration. Results: The absolute spin concentration could be quantified with a precision and accuracy better than +/- 10 mu M (k = 1). The spin concentration of samples stored at -80 degrees C could be reproduced after 6 months of storage well within the same error estimate. Conclusion: The absolute spin concentration in wet biological samples such as biopsies, water solutions and cell cultures could be quantified with higher precision and accuracy than normally achievable using common techniques such as flat cells, tissue cells and various capillary tubes. In addition; biological samples could be collected and stored for future incubation with spin probe, and also further stored up to at least six months before EPR analysis, without loss of signal intensity. This opens for the possibility to store and transport incubated biological samples with known accuracy of the spin concentration over time.

  • 43.
    Berg, Lotta
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Andersson, C. David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Artursson, Elisabet
    Hornberg, Andreas
    Tunemalm, Anna-Karin
    Linusson, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Ekstrom, Fredrik
    Targeting Acetylcholinesterase: Identification of Chemical Leads by High Throughput Screening, Structure Determination and Molecular Modeling2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 11, artikel-id e26039Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by rapid hydrolysis of the neurotransmitter acetylcholine. Compounds inhibiting this enzyme can be used (inter alia) to treat cholinergic deficiencies (e. g. in Alzheimer's disease), but may also act as dangerous toxins (e. g. nerve agents such as sarin). Treatment of nerve agent poisoning involves use of antidotes, small molecules capable of reactivating AChE. We have screened a collection of organic molecules to assess their ability to inhibit the enzymatic activity of AChE, aiming to find lead compounds for further optimization leading to drugs with increased efficacy and/or decreased side effects. 124 inhibitors were discovered, with considerable chemical diversity regarding size, polarity, flexibility and charge distribution. An extensive structure determination campaign resulted in a set of crystal structures of protein-ligand complexes. Overall, the ligands have substantial interactions with the peripheral anionic site of AChE, and the majority form additional interactions with the catalytic site (CAS). Reproduction of the bioactive conformation of six of the ligands using molecular docking simulations required modification of the default parameter settings of the docking software. The results show that docking-assisted structure-based design of AChE inhibitors is challenging and requires crystallographic support to obtain reliable results, at least with currently available software. The complex formed between C5685 and Mus musculus AChE (C5685.mAChE) is a representative structure for the general binding mode of the determined structures. The CAS binding part of C5685 could not be structurally determined due to a disordered electron density map and the developed docking protocol was used to predict the binding modes of this part of the molecule. We believe that chemical modifications of our discovered inhibitors, biochemical and biophysical characterization, crystallography and computational chemistry provide a route to novel AChE inhibitors and reactivators.

  • 44.
    Berggren, Hanna
    et al.
    Linnéuniversitetet, Institutionen för biologi och miljö (BOM).
    Nordahl, Oscar
    Linnéuniversitetet, Institutionen för biologi och miljö (BOM).
    Tibblin, Petter
    Linnéuniversitetet, Institutionen för biologi och miljö (BOM).
    Larsson, Per
    Linnéuniversitetet, Institutionen för biologi och miljö (BOM).
    Forsman, Anders
    Linnéuniversitetet, Institutionen för biologi och miljö (BOM).
    Testing for local adaptation to spawning habitat in sympatric subpopulations of pike by reciprocal translocation of embryos2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 5, artikel-id e0154488Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We tested for local adaption in early life-history traits by performing a reciprocal translocation experiment with approximately 2,500 embryos of pike (Esox lucius) divided in paired split-family batches. The experiment indicated local adaptation in one of the two subpopulations manifested as enhanced hatching success of eggs in the native habitat, both when compared to siblings transferred to a non-native habitat, and when compared to immigrant genotypes from the other subpopulation. Gene-by-environment effects on viability of eggs and larvae were evident in both subpopulations, showing that there existed genetic variation allowing for evolutionary responses to divergent selection, and indicating a capacity for plastic responses to environmental change. Next, we tested for differences in female life-history traits. Results uncovered that females from one population invested more resources into reproduction and also produced more (but smaller) eggs in relation to their body size compared to females from the other population. We suggest that these females have adjusted their reproductive strategies as a counter-adaptation because a high amount of sedimentation on the eggs in that subpopulations spawning habitat might benefit smaller eggs. Collectively, our findings point to adaptive divergence among sympatric subpopulations that are physically separated only for a short period during reproduction and early development-which is rare. These results illustrate how combinations of translocation experiments and field studies of life-history traits might infer about local adaptation and evolutionary divergence among populations. Local adaptations in subdivided populations are important to consider in management and conservation of biodiversity, because they may otherwise be negatively affected by harvesting, supplementation, and reintroduction efforts targeted at endangered populations.

  • 45. Berggren, Martin
    et al.
    Bergström, Ann-Kristin
    Karlsson, Jan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Intraspecific Autochthonous and Allochthonous Resource Use by Zooplankton in a Humic Lake during the Transitions between Winter, Summer and Fall2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 3, artikel-id e0120575Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Seasonal patterns in assimilation of externally produced, allochthonous, organic matter into aquatic food webs are poorly understood, especially in brown-water lakes. We studied the allochthony (share biomass of terrestrial origin) in cladoceran, calanoid and cyclopoid micro-crustacean zooplankton from late winter to fall during two years in a small humic lake (Sweden). The use of allochthonous resources was important for sustaining a small population of calanoids in the water column during late winter. However, in summer the calanoids shifted to 100% herbivory, increasing their biomass several-fold by making efficient use of the pelagic primary production. In contrast, the cyclopoids and cladocerans remained at high levels of allochthony throughout the seasons, both groups showing the mean allochthony of 0.56 (range in mean 0.17-0.79 and 0.34-0.75, for the respective group, depending on model parameters). Our study shows that terrestrial organic matter can be an important resource for cyclopoids and cladocerans on an annual basis, forming a significant link between terrestrial organic matter and the higher trophic levels of the food web, but it can also be important for sustaining otherwise herbivorous calanoids during periods of low primary production in late winter.

  • 46. Berglund, Björn
    et al.
    Khan, Ghazanfar Ali
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindberg, Richard
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Fick, Jerker
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Lindgren, Per-Eric
    Abundance and dynamics of antibiotic resistance genes and integrons in lake sediment microcosms2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 9, artikel-id e108151Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antibiotic resistance in bacteria causing disease is an ever growing threat to the world. Recently, environmental bacteria have become established as important both as sources of antibiotic resistance genes and in disseminating resistance genes. Low levels of antibiotics and other pharmaceuticals are regularly released into water environments via wastewater, and the concern is that such environmental contamination may serve to create hotspots for antibiotic resistance gene selection and dissemination. In this study, microcosms were created from water and sediments gathered from a lake in Sweden only lightly affected by human activities. The microcosms were exposed to a mixture of antibiotics of varying environmentally relevant concentrations (i.e., concentrations commonly encountered in wastewaters) in order to investigate the effect of low levels of antibiotics on antibiotic resistance gene abundances and dynamics in a previously uncontaminated environment. Antibiotic concentrations were measured using liquid chromatography-tandem mass spectrometry. Abundances of seven antibiotic resistance genes and the class 1 integron integrase gene, intL1, were quantified using real-time PCR. Resistance genes sulI and ermB were quantified in the microcosm sediments with mean abundances 5 and 15 gene copies/10(6) 16S rRNA gene copies, respectively. Class 1 integrons were determined in the sediments with a mean concentration of 3.86x10(4) copies/10(6) 16S rRNA gene copies. The antibiotic treatment had no observable effect on antibiotic resistance gene or integron abundances.

  • 47.
    Berglund, Åsa MM
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Rainio, Miia J
    Eeva, Tapio
    Temporal trends in metal pollution: using bird excrement as indicator2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 2, artikel-id e0117071Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Past mining and smelting activities have resulted in metal polluted environments all over the world, but long-term monitoring data is often scarce, especially in higher trophic levels. In this study we used bird (Parus major and Ficedula hypoleuca) excrement to monitor metal pollution in the terrestrial environment following 16 years of continuously reduced emissions from a copper/nickel smelter in Finland. In the early 1990s, lead and cadmium concentrations dropped significantly in excrement, but the reduction did not directly reflect the changes in atmospheric emission from the smelter. This is likely due to a continuous contribution of metals also from the soil pool. We conclude that bird excrement can be used to assess changes in the environment as a whole but not specifically changes in atmospheric emission. Inter-annual variation in excrement concentration of especially copper and nickel demonstrates the importance of long-term monitoring to discern significant trends.

  • 48. Bergman, Inger
    et al.
    Bishop, Kevin
    Tu, Qiang
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Frech, Wolfgang
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Åkerblom, Staffan
    Nilsson, Mats
    The influence of sulphate deposition on the seasonal variation of peat pore water methyl Hg in a boreal mire2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 9, s. e45547-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this paper we investigate the hypothesis that long-term sulphate (SO42-) deposition has made peatlands a larger source of methyl mercury (MeHg) to remote boreal lakes. This was done on experimental plots at a boreal, low sedge mire where the effect of long-term addition of SO42- on peat pore water MeHg concentrations was observed weekly throughout the snow-free portion of 1999. The additions of SO42- started in 1995. The seasonal mean of the pore water MeHg concentrations on the plots with 17 kg ha(-1) yr(-1) of sulphur (S) addition (1.3 +/- 0.08 ng L-1, SE; n=44) was significantly (p<0.0001) higher than the mean MeHg concentration on the plots with 3 kg ha(-1) yr(-1) of ambient S deposition (0.6 +/- 0.02 ng L-1, SE; n=44). The temporal variation in pore water MeHg concentrations during the snow free season was larger in the S-addition plots, with an amplitude of >2 ng L-1 compared to +/-0.5 ng L-1 in the ambient S deposition plots. The concentrations of pore water MeHg in the S-addition plots were positively correlated (r(2)=0.21; p=0.001) to the groundwater level, with the lowest concentrations of MeHg during the period with the lowest groundwater levels. The pore water MeHg concentrations were not correlated to total Hg, DOC concentration or pH. The results from this study indicate that the persistently higher pore water concentrations of MeHg in the S-addition plots are caused by the long-term additions of SO42- to the mire surface. Since these waters are an important source of runoff, the results support the hypothesis that SO42- deposition has increased the contribution of peatlands to MeHg in downstream aquatic systems. This would mean that the increased deposition of SO42- in acid rain has contributed to the modern increase in the MeHg burdens of remote lakes hydrologically connected to peatlands.

  • 49.
    Bernhardsson, Carolina
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Ingvarsson, Pär K
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Molecular population genetics of elicitor-induced resistance genes in European aspen (Populus tremula L., Salicaceae)2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 9, s. e24867-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Owing to their long life span and ecological dominance in many communities, forest trees are subject to attack from a diverse array of herbivores throughout their range, and have therefore developed a large number of both constitutive and inducible defenses. We used molecular population genetics methods to examine the evolution of eight genes in European aspen, Populus tremula, that are all associated with defensive responses against pests and/or pathogens, and have earlier been shown to become strongly up-regulated in poplars as a response to wounding and insect herbivory. Our results show that the majority of these defense genes show patterns of intraspecific polymorphism and site-frequency spectra that are consistent with a neutral model of evolution. However, two of the genes, both belonging to a small gene family of polyphenol oxidases, show multiple deviations from the neutral model. The gene PPO1 has a 600 bp region with a highly elevated K(A)/K(S) ratio and reduced synonymous diversity. PPO1 also shows a skew toward intermediate frequency variants in the SFS, and a pronounced fixation of non-synonymous mutations, all pointing to the fact that PPO1 has been subjected to recurrent selective sweeps. The gene PPO2 shows a marked excess of high frequency, derived variants and shows many of the same trends as PPO1 does, even though the pattern is less pronounced, suggesting that PPO2 might have been the target of a recent selective sweep. Our results supports data from both Populus and other species which have found that the the majority of defense-associated genes show few signs of selection but that a number of genes involved in mediating defense against herbivores show signs of adaptive evolution.

  • 50. Berthelot, Claire C
    et al.
    Kamita, Shizuo George
    Sacchi, Romina
    Yang, Jun
    Nording, Malin L
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Department of Entomology, University of California Davis, Davis, CA, United States Of America.
    Georgi, Katrin
    Karbowski, Christine Hegedus
    German, J Bruce
    Weiss, Robert H
    Hogg, Ronald J
    Hammock, Bruce D
    Zivkovic, Angela M
    Changes in PTGS1 and ALOX12 Gene Expression in Peripheral Blood Mononuclear Cells Are Associated with Changes in Arachidonic Acid, Oxylipins, and Oxylipin/Fatty Acid Ratios in Response to Omega-3 Fatty Acid Supplementation2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 12, artikel-id e0144996Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: There is a high degree of inter-individual variability among people in response to intervention with omega-3 fatty acids (FA), which may partly explain conflicting results on the effectiveness of omega-3 FA for the treatment and prevention of chronic inflammatory diseases. In this study we sought to evaluate whether part of this inter-individual variability in response is related to the regulation of key oxylipin metabolic genes in circulating peripheral blood mononuclear cells (PBMCs). Methods: Plasma FA and oxylipin profiles from 12 healthy individuals were compared to PBMC gene expression profiles following six weeks of supplementation with fish oil, which delivered 1.9 g/d eicosapentaenoic acid (EPA) and 1.5 g/d docosahexaenoic acid (DHA). Fold changes in gene expression were measured by a quantitative polymerase chain reaction (qPCR). Results: Healthy individuals supplemented with omega-3 FA had differential responses in prostaglandin-endoperoxide synthase 1 (PTGS1), prostaglandin-endoperoxide synthase 2 (PTGS2), arachidonate 12-lipoxygenase (ALOX12), and interleukin 8 (IL-8) gene expression in isolated PBMCs. In those individuals for whom plasma arachidonic acid (ARA) in the phosphatidylethanolamine (PE) lipid class decreased in response to omega-3 intervention, there was a corresponding decrease in gene expression for PTGS1 and ALOX12. Several oxylipin product/FA precursor ratios (e.g. prostaglandin E-2 (PGE(2))/ARA for PTGS1 and 12-hydroxyeicosatetraenoic acid (12-HETE)/ARA for ALOX12) were also associated with fold change in gene expression, suggesting an association between enzyme activity and gene expression. The fold-change in PTGS1 gene expression was highly positively correlated with ALOX12 gene expression but not with PTGS2, whereas IL-8 and PTGS2 were positively correlated. Conclusions: The regulation of important oxylipin metabolic genes in PBMCs varied with the extent of change in ARA concentrations in the case of PTGS1 and ALOX12 regulation. PBMC gene expression changes in response to omega-3 supplementation varied among healthy individuals, and were associated with changes in plasma FA and oxylipin composition to different degrees in different individuals.

1234567 1 - 50 av 642
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf