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  • 1.
    Abate, Ebba
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Belayneh, Meseret
    University of Addis Ababa, Ethiopia .
    Gelaw, Aschalew
    University of Gondar, Ethiopia .
    Idh, Jonna
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Getachew, Assefa
    University of Gondar, Ethiopia .
    Alemu, Shitaye
    University of Gondar, Ethiopia .
    Diro, Ermias
    University of Gondar, Ethiopia .
    Fikre, Nigussu
    University of Addis Ababa, Ethiopia .
    Britton, Sven
    Karolinska Hospital, Sweden .
    Elias, Daniel
    University of So Denmark, Denmark .
    Aseffa, Abraham
    Armauer Hansen Research Institute, Ethiopia .
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Schön, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    The Impact of Asymptomatic Helminth Co-Infection in Patients with Newly Diagnosed Tuberculosis in North-West Ethiopia2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 8Article in journal (Refereed)
    Abstract [en]

    Background: Areas endemic of helminth infection, tuberculosis (TB) and HIV are to a large extent overlapping. The aim of this study was to assess the impact of asymptomatic helminth infection on the immunological response among TB patients with and without HIV, their house hold contacts and community controls. less thanbrgreater than less thanbrgreater thanMethodology: Consecutive smear positive TB patients (n = 112), their household contacts (n = 71) and community controls (n = 112) were recruited in Gondar town, Ethiopia. Stool microscopy, HIV serology, serum IgE level, eosinophil and CD4 counts were performed and tuberculosis patients were followed up for 3 months after initiation of anti-TB treatment. less thanbrgreater than less thanbrgreater thanResults: Helminth co-infection rate was 29% in TB patients and 21% in both community control and household contacts (p = 0.3) where Ascaris lumbricoides was the most prevalent parasite. In TB patients the seroprevalence of HIV was 47% (53/112). Eosinophilia and elevated IgE level were significantly associated with asymptomatic helminth infection. During TB treatment, the worm infection rate of HIV+/TB patients declined from 31% (10/32) at week 0 to 9% (3/32) at week 2 of TB treatment, whereas HIV2/TB patients showed no change from baseline to week 2, 29% (13/45) vs. 22.2% (10/45). This trend was stable at week 8 and 12 as well. less thanbrgreater than less thanbrgreater thanConclusion: One third of smear positive TB patients were infected with helminths. Eosinophilia and elevated IgE level correlated with asymptomatic worm infection, indicating an effect on host immunity. The rate of worm infection declined during TB treatment in HIV+/TB co-infected patients whereas no decline was seen in HIV2/TB group.

  • 2. Abbott, Jessica K.
    et al.
    Innocenti, Paolo
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Chippindale, Adam K.
    Morrow, Edward H.
    Epigenetics and Sex-Specific Fitness: An Experimental Test Using Male-Limited Evolution in Drosophila melanogaster2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 7, p. e70493-Article in journal (Refereed)
    Abstract [en]

    When males and females have different fitness optima for the same trait but share loci, intralocus sexual conflict is likely to occur. Epigenetic mechanisms such as genomic imprinting (in which expression is altered according to parent-of-origin) and sex-specific maternal effects have been suggested as ways by which this conflict can be resolved. However these ideas have not yet been empirically tested. We designed an experimental evolution protocol in Drosophila melanogaster that enabled us to look for epigenetic effects on the X-chromosome-a hotspot for sexually antagonistic loci. We used special compound-X females to enforce father-to-son transmission of the X-chromosome for many generations, and compared fitness and gene expression levels between Control males, males with a Control X-chromosome that had undergone one generation of father-son transmission, and males with an X-chromosome that had undergone many generations of father-son transmission. Fitness differences were dramatic, with experimentally-evolved males approximately 20% greater than controls, and with males inheriting a non-evolved X from their father about 20% lower than controls. These data are consistent with both strong intralocus sexual conflict and misimprinting of the X-chromosome under paternal inheritance. However, expression differences suggested that reduced fitness under paternal X inheritance was largely due to deleterious maternal effects. Our data confirm the sexually-antagonistic nature of Drosophila's X-chromosome and suggest that the response to male-limited X-chromosome evolution entails compensatory evolution for maternal effects, and perhaps modification of other epigenetic effects via coevolution of the sex chromosomes.

  • 3.
    Abdelfattah, Ahmed
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Università Mediterranea di Reggio Calabria, Italy.
    Ruano-Rosa, David
    Cacciola, Santa Olga
    Nicosia, Maria G. Li Destri
    Schena, Leonardo
    Impact of Bactrocera oleae on the fungal microbiota of ripe olive drupes2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 11, article id e0199403Article in journal (Refereed)
    Abstract [en]

    The olive fruit fly (OFF), Bactrocera oleae is the most devastating pest affecting olive fruit worldwide. Previous investigations have addressed the fungal microbiome associated with olive drupes or B. oleae, but the impact of the insect on fungal communities of olive fruit remains undescribed. In the present work, the fungal microbiome of olive drupes, infested and non-infested by the OFF, was investigated in four different localities and cultivars. Olive fruit fly infestations caused a general reduction of the fungal diversity, a higher quantity of the total DNA and an increase in taxa that remained unidentified or had unknown roles. The infestations led to imbalanced fungal communities with the growth of taxa that are usually outcompeted. While it was difficult to establish a cause-effect link between fly infestation and specific fungi, it is clear that the fly alters the natural microbial balance, especially the low abundant taxa. On the other hand, the most abundant ones, were not significantly influenced by the insect. In fact, despite the slight variation between the sampling locations, Aureobasidium, Cladosporium, and Alternaria, were the dominant genera, suggesting the existence of a typical olive fungal microbiome.

  • 4.
    Abdelrahman, Islam
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Elmasry, Moustafa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Plastic Surgery Unit, Surgery Department, Suez Canal University, Ismailia, Egypt.
    Olofsson, Pia
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Hand and Plastic Surgery. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Division of overall duration of stay into operative stay and postoperative stay improves the overall estimate as a measure of quality of outcome in burn care.2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0174579Article in journal (Refereed)
    Abstract [en]

    Patients and Methods: Surgically managed burn patients admitted between 2010-14 were included. Operative stay was defined as the time from admission until the last operation, postoperative stay as the time from the last operation until discharge. The difference in variation was analysed with F-test. A retrospective review of medical records was done to explore reasons for extended postoperative stay. Multivariable regression was used to assess factors associated with operative stay and postoperative stay.less thanbr /greater thanResults: Operative stay/TBSA% showed less variation than total duration/TBSA% (F test = 2.38, pless than0.01). The size of the burn, and the number of operations, were the independent factors that influenced operative stay (R2 0.65). Except for the size of the burn other factors were associated with duration of postoperative stay: wound related, psychological and other medical causes, advanced medical support, and accommodation arrangements before discharge, of which the two last were the most important with an increase of (mean) 12 and 17 days (pless than0.001, R2 0.51).less thanbr /greater thanConclusion: Adjusted operative stay showed less variation than total hospital stay and thus can be considered a more accurate outcome measure for surgically managed burns. The size of burn and number of operations are the factors affecting this outcome measure.

  • 5.
    Abdgawad, Mohamed
    et al.
    Lund University.
    Pettersson, Asa
    Lund University.
    Gunnarsson, Lena
    Lund University.
    Bengtsson, Anders A
    Lund University.
    Geborek, Pierre
    Lund University.
    Nilsson, Lars
    Lund University.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Pharmacology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL.
    Hellmark, Thomas
    Lund University.
    Decreased Neutrophil Apoptosis in Quiescent ANCA-Associated Systemic Vasculitis2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 3Article in journal (Refereed)
    Abstract [en]

    Background: ANCA-Associated Systemic Vasculitis (AASV) is characterized by leukocytoclasis, accumulation of unscavenged apoptotic and necrotic neutrophils in perivascular tissues. Dysregulation of neutrophil cell death may contribute directly to the pathogenesis of AASV. less thanbrgreater than less thanbrgreater thanMethods: Neutrophils from Healthy Blood Donors (HBD), patients with AASV most in complete remission, Polycythemia Vera (PV), Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA) and renal transplant recipients (TP) were incubated in vitro, and the rate of spontaneous apoptosis was measured by FACS. Plasma levels of cytokines and sFAS were measured with cytometric bead array and ELISA. Expression of pro/anti-apoptotic factors, transcription factors C/EBP-alpha, C/EBP-beta and PU.1 and inhibitors of survival/JAK2-pathway were measured by real-time-PCR. less thanbrgreater than less thanbrgreater thanResults: AASV, PV and RA neutrophils had a significantly lower rate of apoptosis compared to HBD neutrophils (AASV 50 +/- 14% vs. HBD 64 +/- 11%, p andlt; 0.0001). In RA but not in AASV and PV, low apoptosis rate correlated with increased plasma levels of GM-CSF and high mRNA levels of anti-apoptotic factors Bcl-2A1 and Mcl-1. AASV patients had normal levels of G-CSF, GM-CSF and IL-3. Both C/EBP-alpha, C/EBP-beta were significantly higher in neutrophils from AASV patients than HBD. Levels of sFAS were significantly higher in AASV compared to HBD. less thanbrgreater than less thanbrgreater thanConclusion: Neutrophil apoptosis rates in vitro are decreased in AASV, RA and PV but mechanisms seem to differ. Increased mRNA levels of granulopoiesis-associated transcription factors and increased levels of sFAS in plasma were observed in AASV. Additional studies are required to define the mechanisms behind the decreased apoptosis rates, and possible connections with accumulation of dying neutrophils in regions of vascular lesions in AASV patients.

  • 6.
    Abdul-Hussein, Saba
    et al.
    Department of Pathology, University of Gothenburg, Gothenburg, Sweden.
    Rahl, Karin
    Department of Pathology, University of Gothenburg, Gothenburg, Sweden.
    Moslemi, Ali-Reza
    Department of Pathology, University of Gothenburg, Gothenburg, Sweden.
    Tajsharghi, Homa
    Department of Pathology, University of Gothenburg, Gothenburg, Sweden / Department of Clinical and Medical Genetics, University of Gothenburg, Gothenburg, Sweden.
    Phenotypes of myopathy-related beta-tropomyosin mutants in human and mouse tissue cultures2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, article id e72396Article in journal (Refereed)
    Abstract [en]

    Mutations in TPM2 result in a variety of myopathies characterised by variable clinical and morphological features. We used human and mouse cultured cells to study the effects of β-TM mutants. The mutants induced a range of phenotypes in human myoblasts, which generally changed upon differentiation to myotubes. Human myotubes transfected with the E41K-β-TM(EGFP) mutant showed perinuclear aggregates. The G53ins-β-TM(EGFP) mutant tended to accumulate in myoblasts but was incorporated into filamentous structures of myotubes. The K49del-β-TM(EGFP) and E122K-β-TM(EGFP) mutants induced the formation of rod-like structures in human cells. The N202K-β-TM(EGFP) mutant failed to integrate into thin filaments and formed accumulations in myotubes. The accumulation of mutant β-TM(EGFP) in the perinuclear and peripheral areas of the cells was the striking feature in C2C12. We demonstrated that human tissue culture is a suitable system for studying the early stages of altered myofibrilogenesis and morphological changes linked to myopathy-related β-TM mutants. In addition, the histopathological phenotype associated with expression of the various mutant proteins depends on the cell type and varies with the maturation of the muscle cell. Further, the phenotype is a combinatorial effect of the specific amino acid change and the temporal expression of the mutant protein.

  • 7. Abel, Olubunmi
    et al.
    Powell, John F
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Al-Chalabi, Ammar
    Credibility analysis of putative disease-causing genes using bioinformatics2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e64899-Article in journal (Refereed)
    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.

  • 8. Aboagye, Emmanuel
    et al.
    Hagberg, Jan
    Axén, Iben
    Kwak, Lydia
    Lohela-Karlsson, Malin
    Skillgate, Eva
    Dahlgren, Gunilla
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jensen, Irene
    Individual preferences for physical exercise as secondary prevention for non-specific low back pain: a discrete choice experiment2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 12, article id e0187709Article in journal (Refereed)
    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.

  • 9.
    Abraha, Atakelti
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Tigray Health Bureau, Tigray and Ethiopian Health Insurance Agency, Addis Ababa, Ethiopia.
    Myléus, Anna
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Byass, Peter
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. 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 University, Faculty of Medicine, Department of Public Health and Clinical Medicine. 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, Ethiopia2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 6, article id e0218101Article in journal (Refereed)
    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.

  • 10.
    Abramenkovs, Andris
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Stenerlöw, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medical Radiation Science.
    Removal of heat-sensitive clustered damaged DNA sites is independent of double-strand break repair2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0209594Article in journal (Refereed)
    Abstract [en]

    DNA double-strand breaks (DSBs) are the most deleterious lesions that can arise in cells after ionizing radiation or radiometric drug treatment. In addition to prompt DSBs, DSBs may also be produced during repair, evolving from a clustered DNA damaged site, which is composed of two or more distinct lesions that are located within two helical turns. A specific type of cluster damage is the heat-sensitive clustered site (HSCS), which transforms into DSBs upon treatment at elevated temperatures. The actual lesions or mechanisms that mediate the HSCS transformation into DSBs are unknown. However, there are two possibilities; either these lesions are transformed into DSBs due to DNA lesion instability, e.g., transfer of HSCS into single-strand breaks (SSBs), or they are formed due to local DNA structure instability, e.g., DNA melting, where two SSBs on opposite strands meet and transform into a DSB. The importance of these processes in living cells is not understood, but they significantly affect estimates of DSB repair capacity. In this study, we show that HSCS removal in human cells is not affected by defects in DSB repair or inhibition of DSB repair. Under conditions where rejoining of prompt DSBs was almost completely inhibited, heat-sensitive DSBs were successfully rejoined, without resulting in increased DSB levels, indicating that HSCS do not transfer into DSB in cells under physiological conditions. Furthermore, analysis by atomic force microscopy suggests that prolonged heating of chromosomal DNA can induce structural changes that facilitate transformation of HSCS into DSB. In conclusion, the HSCS do not generate additional DSBs at physiological temperatures in human cells, and the repair of HSCS is independent of DSB repair.

  • 11.
    Acerbi, Alberto
    et al.
    Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution.
    Ghirlanda, Stefano
    Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution.
    Enquist, Magnus
    Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution. Stockholm University, Faculty of Science, Department of Zoology.
    The logic of fashion cycles2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 3, p. e32541-Article in journal (Refereed)
    Abstract [en]

    Many cultural traits exhibit volatile dynamics, commonly dubbed fashions or fads. Here we show that realistic fashion-like dynamics emerge spontaneously if individuals can copy others' preferences for cultural traits as well as traits themselves. We demonstrate this dynamics in simple mathematical models of the diffusion, and subsequent abandonment, of a single cultural trait which individuals may or may not prefer. We then simulate the coevolution between many cultural traits and the associated preferences, reproducing power-law frequency distributions of cultural traits (most traits are adopted by few individuals for a short time, and very few by many for a long time), as well as correlations between the rate of increase and the rate of decrease of traits (traits that increase rapidly in popularity are also abandoned quickly and vice versa). We also establish that alternative theories, that fashions result from individuals signaling their social status, or from individuals randomly copying each other, do not satisfactorily reproduce these empirical observations.

  • 12.
    Acerbi, Alberto
    et al.
    Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution. University of Bristol, United Kingdom.
    Lampos, Vasileios
    Garnett, Philip
    Bentley, R. Alexander
    The Expression of Emotions in 20th Century Books2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 3, article id e59030Article in journal (Refereed)
    Abstract [en]

    We report here trends in the usage of mood words, that is, words carrying emotional content, in 20th century English language books, using the data set provided by Google that includes word frequencies in roughly 4% of all books published up to the year 2008. We find evidence for distinct historical periods of positive and negative moods, underlain by a general decrease in the use of emotion-related words through time. Finally, we show that, in books, American English has become decidedly more emotional than British English in the last half-century, as a part of a more general increase of the stylistic divergence between the two variants of English language.

  • 13.
    Acuna, Lillian G.
    et al.
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Pablo Cardenas, Juan
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Covarrubias, Paulo C.
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Jose Haristoy, Juan
    Fundación Ciencia & Vida, Chile.
    Flores, Rodrigo
    Fundación Ciencia & Vida, Chile.
    Nuñez, Harold
    Fundación Ciencia & Vida, Chile.
    Riadi, Gonzalo
    Universidad de Talca, Chile.
    Shmaryahu, Amir
    Fundación Ciencia & Vida, Chile.
    Valdes, Jorge
    Center for Systems Biotechnology, Chile.
    Dopson, Mark
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Rawlings, Douglas E.
    University of Stellenbosch, South Africa.
    Banfield, Jillian F.
    University of California, USA.
    Holmes, David S.
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Quatrini, Raquel
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Architecture and Gene Repertoire of the Flexible Genome of the Extreme Acidophile Acidithiobacillus caldus2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, article id e78237Article in journal (Refereed)
    Abstract [en]

    Background: Acidithiobacillus caldus is a sulfur oxidizing extreme acidophile and the only known mesothermophile within the Acidithiobacillales. As such, it is one of the preferred microbes for mineral bioprocessing at moderately high temperatures. In this study, we explore the genomic diversity of A. caldus strains using a combination of bioinformatic and experimental techniques, thus contributing first insights into the elucidation of the species pangenome. Principal Findings: Comparative sequence analysis of A. caldus ATCC 51756 and SM-1 indicate that, despite sharing a conserved and highly syntenic genomic core, both strains have unique gene complements encompassing nearly 20% of their respective genomes. The differential gene complement of each strain is distributed between the chromosomal compartment, one megaplasmid and a variable number of smaller plasmids, and is directly associated to a diverse pool of mobile genetic elements (MGE). These include integrative conjugative and mobilizable elements, genomic islands and insertion sequences. Some of the accessory functions associated to these MGEs have been linked previously to the flexible gene pool in microorganisms inhabiting completely different econiches. Yet, others had not been unambiguously mapped to the flexible gene pool prior to this report and clearly reflect strain-specific adaption to local environmental conditions. Significance: For many years, and because of DNA instability at low pH and recurrent failure to genetically transform acidophilic bacteria, gene transfer in acidic environments was considered negligible. Findings presented herein imply that a more or less conserved pool of actively excising MGEs occurs in the A. caldus population and point to a greater frequency of gene exchange in this econiche than previously recognized. Also, the data suggest that these elements endow the species with capacities to withstand the diverse abiotic and biotic stresses of natural environments, in particular those associated with its extreme econiche.

  • 14.
    Adamo, Hanibal Hani
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergström, Sofia Halin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Characterization of a Gene Expression Signature in Normal Rat Prostate Tissue Induced by the Presence of a Tumor Elsewhere in the Organ2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, article id e0130076Article in journal (Refereed)
    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.

  • 15.
    Adamo, Hanibal Hani
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Strömvall, Kerstin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 11, article id e0141601Article in journal (Refereed)
    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.

  • 16. Adem, Abdu
    et al.
    Al Haj, Mahmoud
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Benedict, Sheela
    Yasin, Javed
    Nagelkerke, Nicolas
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Yandle, Tim G.
    Frampton, Chris M.
    Lewis, Lynley K.
    Nicholls, M. Gary
    Kazzam, Elsadig
    ANP and BNP Responses to Dehydration in the One-Humped Camel and Effects of Blocking the Renin-Angiotensin System2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 3, p. e57806-Article in journal (Refereed)
    Abstract [en]

    The objectives of this study were to investigate and compare the responses of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in the circulation of hydrated, dehydrated, and dehydrated losartan - treated camels; and to document the cardiac storage form of B-type natriuretic peptide in the camel heart. Eighteen male camels were used in the study: control or hydrated camels (n = 6), dehydrated camels (n = 6) and dehydrated losartan-treated camels (n = 6) which were dehydrated and received the angiotensin II (Ang II) AT-1 receptor blocker, losartan, at a dose of 5 mg/kg body weight intravenously for 20 days. Control animals were supplied with feed and water ad-libitum while both dehydrated and dehydrated-losartan treated groups were supplied with feed ad-libitum but no water for 20 days. Compared with time-matched controls, dehydrated camels exhibited a significant decrease in plasma levels of both ANP and BNP. Losartan-treated camels also exhibited a significant decline in ANP and BNP levels across 20 days of dehydration but the changes were not different from those seen with dehydration alone. Size exclusion high performance liquid chromatography of extracts of camel heart indicated that proB-type natriuretic peptide is the storage form of the peptide. We conclude first, that dehydration in the camel induces vigorous decrements in circulating levels of ANP and BNP; second, blockade of the renin-angiotensin system has little or no modulatory effect on the ANP and BNP responses to dehydration; third, proB-type natriuretic peptide is the storage form of this hormone in the heart of the one-humped camel.

  • 17.
    Adler, Jeremy
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Parmryd, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Quantifying colocalization: thresholding, void voxels and the H-coef2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, p. e111983-Article in journal (Refereed)
    Abstract [en]

    A critical step in the analysis of images is identifying the area of interest e.g. nuclei. When the nuclei are brighter than the remainder of the image an intensity can be chosen to identify the nuclei. Intensity thresholding is complicated by variations in the intensity of individual nuclei and their intensity relative to their surroundings. To compensate thresholds can be based on local rather than global intensities. By testing local thresholding methods we found that the local mean performed poorly while the Phansalkar method and a new method based on identifying the local background were superior. A new colocalization coefficient, the Hcoef, highlights a number of controversial issues. (i) Are molecular interactions measurable (ii) whether to include voxels without fluorophores in calculations, and (iii) the meaning of negative correlations. Negative correlations can arise biologically (a) because the two fluorophores are in different places or (b) when high intensities of one fluorophore coincide with low intensities of a second. The cases are distinct and we argue that it is only relevant to measure correlation using pixels that contain both fluorophores and, when the fluorophores are in different places, to just report the lack of co-occurrence and omit these uninformative negative correlation. The Hcoef could report molecular interactions in a homogenous medium. But biology is not homogenous and distributions also reflect physico-chemical properties, targeted delivery and retention. The Hcoef actually measures a mix of correlation and co-occurrence, which makes its interpretation problematic and in the absence of a convincing demonstration we advise caution, favouring separate measurements of correlation and of co-occurrence.

  • 18.
    Aeinehband, Shahin
    et al.
    Karolinska Institutet.
    Lindblom, Rickard P. F.
    Karolinska Institutet.
    Al Nimer, Faiez
    Karolinska Institutet.
    Vijayaraghavan, Swetha
    Karolinska Institutet.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Khademi, Mohsen
    Karolinska Institutet.
    Olsson, Tomas
    Karolinska Institutet.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Darreh-Shori, Taher
    Karolinska Institutet.
    Piehl, Fredrik
    Karolinska Institutet.
    Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0122048Article in journal (Refereed)
    Abstract [en]

    Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genomewide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with >= 9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.

  • 19. Aeinehband, Shahin
    et al.
    Lindblom, Rickard P F
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Al Nimer, Faiez
    Vijayaraghavan, Swetha
    Sandholm, Kerstin
    Khademi, Mohsen
    Olsson, Tomas
    Nilsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Nilsson, Kristina Ekdahl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Darreh-Shori, Taher
    Piehl, Fredrik
    Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4Article in journal (Refereed)
    Abstract [en]

    Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genomewide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with >= 9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.

  • 20.
    Agebratt, Christian
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ström, Edvin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Romu, Thobias
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Leandersson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content, Cardiovascular Risk Factors and Basal Metabolic Rate2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 1, p. e0147149-Article in journal (Refereed)
    Abstract [en]

    Background

    Fruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern.

    Objectives

    To study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans.

    Methods

    Thirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers.

    Results

    Weight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15±1.61 kg/m2 to 22.30±1.7 kg/m2, p = 0.24 nuts: from 22.54±2.26 kg/m2 to 22.73±2.28 kg/m2, p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519±721 kcal/day to 2763±595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1±6.0 gram/day to 25.6±9.6 gram/day, p<0.0001, nuts: from 12.4±5.7 gram/day to 6.5±5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistical significant only in the fruit group (from 7.73±3.1 pmol/l to 8.81±2.9 pmol/l, p = 0.018, nuts: from 7.29±2.9 pmol/l to 8.62±3.0 pmol/l, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group.

    Conclusions

    Although BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI.

  • 21.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, Faculty of Science & Engineering.
    Effects of Divergent Selection for Fear of Humans on Behaviour in Red Junglefowl2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, p. 1-12Article in journal (Refereed)
    Abstract [en]

    Domestication has caused a range of similar phenotypic changes across taxa, relating to physiology, morphology and behaviour. It has been suggested that this recurring domesticated phenotype may be a result of correlated responses to a central trait, namely increased tameness. We selected Red Junglefowl, the ancestors of domesticated chickens, during five generations for reduced fear of humans. This caused a marked and significant response in tameness, and previous studies have found correlated effects on growth, metabolism, reproduction, and some behaviour not directly selected for. Here, we report the results from a series of behavioural tests carried out on the initial parental generation (P0) and the fifth selected generation (S5), focusing on behaviour not functionally related to tameness, in order to study any correlated effects. Birds were tested for fear of humans, social reinstatement tendency, open field behaviour at two different ages, foraging/exploration, response to a simulated aerial predator attack and tonic immobility. In S5, there were no effects of selection on foraging/exploration or tonic immobility, while in the social reinstatement and open field tests there were significant interactions between selection and sex. In the aerial predator test, there were significant main effects of selection, indicating that fear of humans may represent a general wariness towards predators. In conclusion, we found only small correlated effects on behaviours not related to the tameness trait selected for, in spite of them showing high genetic correlations to fear of humans in a previous study on the same population. This suggests that species-specific behaviour is generally resilient to changes during domestication.

  • 22.
    Agnvall, Beatrix
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Jöngren, Markus
    Linköping University, Department of Physics, Chemistry and Biology, Biology. Linköping University, The Institute of Technology.
    Strandberg, Erling
    Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Jensen, Per
    Linköping University, Department of Physics, Chemistry and Biology, Zoology. Linköping University, The Institute of Technology.
    Heritability and Genetic Correlations of Fear-Related Behaviour in Red Jungelfowl -Possible Implications for Early Domestication2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, p. e35162-Article in journal (Refereed)
    Abstract [en]

    Domesticated species differ from their wild ancestors in a number of traits, generally referred to as the domesticated phenotype. Reduced fear of humans is assumed to have been an early prerequisite for the successful domestication of virtually all species. We hypothesized that fear of humans is linked to other domestication related traits. For three generations, we selected Red Junglefowl (ancestors of domestic chickens) solely on the reaction in a standardized Fear of Human-test. In this, the birds were exposed for a gradually approaching human, and their behaviour was continuously scored. This generated three groups of animals, high (H), low (L) and intermediate (I) fearful birds. The birds in each generation were additionally tested in a battery of behaviour tests, measuring aspects of fearfulness, exploration, and sociality. The results demonstrate that the variation in fear response of Red Junglefowl towards humans has a significant genetic component and is genetically correlated to behavioural responses in other contexts, of which some are associated with fearfulness and others with exploration. Hence, selection of Red Junglefowl on low fear for humans can be expected to lead to a correlated change of other behavioural traits over generations. It is therefore likely that domestication may have caused an initial suite of behavioural modifications, even without selection on anything besides tameness.

  • 23. 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 University, Faculty of Medicine, Department of Odontology.
    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 Study2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, p. e113160-Article in journal (Refereed)
    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.

  • 24.
    Aguilar, Ximena
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Blomberg, Jeanette
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Brännström, Kristoffer
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Olofsson, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Schleucher, Jurgen
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Björklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Interaction Studies of the Human and Arabidopsis thaliana Med25-ACID Proteins with the Herpes Simplex Virus VP16-and Plant-Specific Dreb2a Transcription Factors2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 5, p. e98575-Article in journal (Refereed)
    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.

  • 25.
    Ahlborg, Mikael
    et al.
    Halmstad University, School of Health and Welfare, Centre of Research on Welfare, Health and Sport (CVHI).
    Svedberg, Petra
    Halmstad University, School of Health and Welfare, Centre of Research on Welfare, Health and Sport (CVHI).
    Nyholm, Maria
    Halmstad University, School of Health and Welfare, Centre of Research on Welfare, Health and Sport (CVHI).
    Morgan, Antony
    Halmstad University, School of Health and Welfare, Centre of Research on Welfare, Health and Sport (CVHI). Glasgow Caledonian University in London, London, United Kingdom.
    Nygren, Jens M.
    Halmstad University, School of Health and Welfare, Centre of Research on Welfare, Health and Sport (CVHI).
    Into the realm of social capital for adolescents: A latent profile analysis2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 2, article id e0212564Article in journal (Refereed)
    Abstract [en]

    Background

    Recent reports of increasing prevalence of frequent health complaints and mental health problems among adolescents call for directing more attention on determinants of adolescent health. The relationship between health and social capital has gained increased attention since the early 2000’s and research at review level confirms the importance of social capital for health outcomes, despite methodological heterogeneity. The aim of this study was to identify distinct profiles of family, school and peer social capital in a nationally representative sample of adolescents and to explore health outcomes in those profiles.

    Method

    Cross-sectional data from the Swedish Health Behaviour of School-aged Children 2013/14 was used for this study. The analytical sample consisted of 7,804 adolescents aged 11-, 13- and 15-years. Items representing sense of belonging and emotional support were assessed in three contexts; family, school and among peers. Latent profile analyses (LPA) were run to determine social capital profiles. Health outcomes included frequent health complaints and life satisfaction, while socioeconomic status and genders were included as predictors.

    Results

    The results show that five distinct profiles best represent the data for 11- and 15-year olds, while a four-profile model was optimal for 13-year olds. Some profiles were recurrent between age groups but unique profiles were also found. Health outcomes were significantly different between profiles depending on levels of social capital in the different contexts.

    Conclusions

    This study provides novel insight into how social capital co-occurs among adolescents within the contexts of family, school and peers and how this translates into differences in health outcomes. The national representativeness of the sample increases the implications of the results and contributes to meaningful insights that help explain the interactions of social capital in multiple contexts, complementing what is previously known about the relationship with adolescent health. © 2019 Ahlborg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

  • 26.
    Ahle, Margareta
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Drott, Peder
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Elfvin, Anders
    Department of Pediatrics, Institution of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Andersson, Roland E.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Department of Surgery, Ryhov County Hospital, Jönköping, Sweden .
    Maternal, fetal and perinatal factors associated with necrotizing enterocolitis in Sweden: A national case-control study2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, PLoS ONE, ISSN 1932-6203, Vol. 13, no 3, article id e0194352Article in journal (Refereed)
    Abstract [en]

    Objective

    To analyze associations of maternal, fetal, gestational, and perinatal factors with necrotizing enterocolitis in a matched case-control study based on routinely collected, nationwide register data.

    Study design

    All infants born in 1987 through 2009 with a diagnosis of necrotizing enterocolitis in any of the Swedish national health care registers were identified. For each case up to 6 controls, matched for birth year and gestational age, were selected. The resulting study population consisted of 720 cases and 3,567 controls. Information on socioeconomic data about the mother, maternal morbidity, pregnancy related diagnoses, perinatal diagnoses of the infant, and procedures in the perinatal period, was obtained for all cases and controls and analyzed with univariable and multivariable logistic regressions for the whole study population as well as for subgroups according to gestational age.

    Results

    In the study population as a whole, we found independent positive associations with necrotizing enterocolitis for isoimmunization, fetal distress, cesarean section, neonatal bacterial infection including sepsis, erythrocyte transfusion, persistent ductus arteriosus, cardiac malformation, gastrointestinal malformation, and chromosomal abnormality. Negative associations were found for maternal weight, preeclampsia, maternal urinary infection, premature rupture of the membranes, and birthweight. Different patterns of associations were seen in the subgroups of different gestational age.

    Conclusion

    With some interesting exceptions, especially in negative associations, the results of this large, population based study, are in keeping with earlier studies. Although restrained by the limitations of register data, the findings mirror conceivable pathophysiological processes and underline that NEC is a multifactorial disease.

  • 27.
    Ahlgren, Kerstin M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Landegren, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    von Euler, Henrik
    Sundberg, Katarina
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lobell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hedhammar, Åke
    Andersson, Göran
    Hansson-Hamlin, Helene
    Lernmark, Åke
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 8, p. e105473-Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS:

    Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.

    METHODS:

    Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide.

    RESULTS:

    None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted.

    CONCLUSIONS/INTERPRETATIONS:

    Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.

  • 28.
    Ahlstrand, Erik
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Medicine, Division of Hematology, Örebro University Hospital, Örebro, Sweden.
    Hellmark, Bengt
    Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Svensson, Karolina
    Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Söderquist, Bo
    Örebro University, School of Medicine, Örebro University, Sweden. Örebro University Hospital. Department of Laboratory Medicine, Clinical Microbiology, Örebro University Hospital, Örebro, Sweden.
    Long-term molecular epidemiology of staphylococcus epidermidis blood culture isolates from patients with hematological malignancies2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, article id e99045Article in journal (Refereed)
    Abstract [en]

    Staphylococcus epidermidis is an important cause of bloodstream infections in patients with hematological malignancies. Knowledge of the long-term epidemiology of these infections is limited. We surveyed all S. epidermidis blood culture isolates from patients treated for hematological malignancies at the University Hospital of Orebro, Sweden from 1980 to 2009. A total of 373 S. epidermidis isolates were identified and multilocus sequence typing, staphylococcal chromosome cassette mec (SCCmec) typing and standard antibiotic susceptibility testing were employed to characterize these isolates. The majority of the isolates 361/373 (97%) belonged to clonal complex 2, and the 373 isolates were divided into 45 sequence types (STs); Simpson's Diversity Index was 0.56. The most prevalent STs were ST2 (243/373, 65%) and ST215 (28/373, 8%). Ninety three percent (226/243) of the ST2 isolates displayed either SCCmec type III or IV. ST2 and 215 were isolated during the entire study period, and together these STs caused temporal peaks in the number of positive blood cultures of S. epidermidis. Methicillin resistance was detected in 213/273 (78%) of all isolates. In the two predominating STs, ST2 and ST215, methicillin resistance was detected in 256/271 isolates (95%), compared with 34/100 (34%) in other STs (p<0.001). In conclusion, in this long-term study of patients with hematological malignancies, we demonstrate a predominance of methicillin-resistant ST2 among S. epidermidis blood culture isolates.

  • 29.
    Ahlén, Gustaf
    et al.
    Recopharma AB.
    Strindelius, Lena
    Recopharma AB.
    Johansson, Tomas
    Recopharma AB.
    Nilsson, Anki
    Rrecopharma AB.
    Chatzissavidou, Nathalie
    Recopharma AB.
    Sjöblom, Magnus
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Rova, Ulrika
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Holsgersson, Jan
    Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy.
    Mannosylated mucin-type immunoglobulin fusion proteins enhance antigen-specific antibody and T lymphocyte responses2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 10Article in journal (Refereed)
    Abstract [en]

    Targeting antigens to antigen-presenting cells (APC) improve their immunogenicity and capacity to induce Th1 responses and cytotoxic T lymphocytes (CTL). We have generated a mucin-type immunoglobulin fusion protein (PSGL-1/mIgG2b), which upon expression in the yeast Pichia pastoris became multivalently substituted with O-linked oligomannose structures and bound the macrophage mannose receptor (MMR) and dendritic cell-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN) with high affinity in vitro. Here, its effects on the humoral and cellular anti-ovalbumin (OVA) responses in C57BL/6 mice are presented.OVA antibody class and subclass responses were determined by ELISA, the generation of anti-OVA CTLs was assessed in 51Cr release assays using in vitro-stimulated immune spleen cells from the different groups of mice as effector cells and OVA peptide-fed RMA-S cells as targets, and evaluation of the type of Th cell response was done by IFN-γ, IL-2, IL-4 and IL-5 ELISpot assays.Immunizations with the OVA − mannosylated PSGL-1/mIgG2b conjugate, especially when combined with the AbISCO®-100 adjuvant, lead to faster, stronger and broader (with regard to IgG subclass) OVA IgG responses, a stronger OVA-specific CTL response and stronger Th1 and Th2 responses than if OVA was used alone or together with AbISCO®-100. Also non-covalent mixing of mannosylated PSGL-1/mIgG2b, OVA and AbISCO®-100 lead to relatively stronger humoral and cellular responses. The O-glycan oligomannoses were necessary because PSGL-1/mIgG2b with mono- and disialyl core 1 structures did not have this effect.Mannosylated mucin-type fusion proteins can be used as versatile APC-targeting molecules for vaccines and as such enhance both humoral and cellular immune responses.

  • 30.
    Ahmad, Irfan
    et al.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan.
    Karah, Nabil
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Nadeem, Aftab
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Uhlin, Bernt Eric
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Analysis of colony phase variation switch in Acinetobacter baumannii clinical isolates2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 1, article id e0210082Article in journal (Refereed)
    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.

  • 31.
    Ahmadi, Zainab
    et al.
    Lund Univ, Div Resp Med & Allergol, Dept Clin Sci, Lund, Sweden.
    Sundh, Josefin
    Univ Orebro, Sch Med Sci, Dept Resp Med, Orebro, Sweden.
    Bornefalk-Hermansson, Anna
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Ekström, Magnus
    Lund Univ, Div Resp Med & Allergol, Dept Clin Sci, Lund, Sweden.
    Long-Term Oxygen Therapy 24 vs 15 h/day and Mortality in Chronic Obstructive Pulmonary Disease2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 9, article id e0163293Article in journal (Refereed)
    Abstract [en]

    Long-term oxygen therapy (LTOT) >= 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease ( COPD). LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day. The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD. This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden. Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids. A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6-2.1). 1,129 (50%) patients died and no patient was lost to follow-up. Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day. LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15-16 h/day in 1,231 (55%) patients. Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality. In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15-16 h/day. A design for a registry-based randomized trial (R-RCT) is proposed.

  • 32.
    Ahmadi, Zainab
    et al.
    Department of Clinical Sciences, Division of Respiratory Medicine & Allergology, Lund University, Lund, Sweden.
    Sundh, Josefin
    Örebro University, School of Medical Sciences. Department of Respiratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Bornefalk-Hermansson, Anna
    Department of Statistics, Uppsala University, Uppsala, Sweden.
    Ekström, Magnus
    Department of Clinical Sciences, Division of Respiratory Medicine & Allergology, Lund University, Lund, Sweden.
    Long-Term Oxygen Therapy 24 vs 15 h/day and Mortality in Chronic Obstructive Pulmonary Disease2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 9, article id e0163293Article in journal (Refereed)
    Abstract [en]

    Long-term oxygen therapy (LTOT) ≥ 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease (COPD). LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day. The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD. This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden. Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids. A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6-2.1). 1,129 (50%) patients died and no patient was lost to follow-up. Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day. LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15-16 h/day in 1,231 (55%) patients. Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality. In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15-16 h/day. A design for a registry-based randomized trial (R-RCT) is proposed.

  • 33. Ahman, Birgitta
    et al.
    Svensson, Kristin
    Rönnegård, Lars
    Dalarna University, School of Technology and Business Studies, Statistics.
    High female mortality resulting in herd collapse in free-ranging domesticated reindeer (Rangifer tarandus tarandus) in Sweden2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 10, article id e111509Article in journal (Refereed)
    Abstract [en]

    Reindeer herding in Sweden is a form of pastoralism practised by the indigenous Sami population. The economy is mainly based on meat production. Herd size is generally regulated by harvest in order not to overuse grazing ranges and keep a productive herd. Nonetheless, herd growth and room for harvest is currently small in many areas. Negative herd growth and low harvest rate were observed in one of two herds in a reindeer herding community in Central Sweden. The herds (A and B) used the same ranges from April until the autumn gathering in October-December, but were separated on different ranges over winter. Analyses of capture-recapture for 723 adult female reindeer over five years (2007-2012) revealed high annual losses (7.1% and 18.4%, for herd A and B respectively). A continuing decline in the total reindeer number in herd B demonstrated an inability to maintain the herd size in spite of a very small harvest. An estimated breakpoint for when herd size cannot be kept stable confirmed that the observed female mortality rate in herd B represented a state of herd collapse. Lower calving success in herd B compared to A indicated differences in winter foraging conditions. However, we found only minor differences in animal body condition between the herds in autumn. We found no evidence that a lower autumn body mass generally increased the risk for a female of dying from one autumn to the next. We conclude that the prime driver of the on-going collapse of herd B is not high animal density or poor body condition. Accidents or disease seem unlikely as major causes of mortality. Predation, primarily by lynx and wolverine, appears to be the most plausible reason for the high female mortality and state of collapse in the studied reindeer herding community.

  • 34. Ahmed, AS
    Alim, MA ()
    Östenson, CG
    Salo, PT
    Hewitt, C
    Hart, DA
    Ackermann, PW
    Compromised Neurotrophic and Angiogenic Regenerative Capability during Tendon Healing in a Rat Model of Type-II Diabetes2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203Article in journal (Refereed)
  • 35.
    Ahmed, B. S.
    et al.
    Istituto Dalle Molle di Studi Sull'Intelligenza Artificiale (IDSIA), Manno-Lugano, Switzerland.
    Sahib, M. A.
    Software and Informatics Engineering Department, Engineering College, Salahaddin University - Erbil, Iraq.
    Gambardella, L. M.
    Istituto Dalle Molle di Studi Sull'Intelligenza Artificiale (IDSIA), Manno-Lugano, Switzerland.
    Afzal, Wasif
    Mälardalen University, School of Innovation, Design and Engineering, Embedded Systems.
    Zamli, K. Z.
    IBM Centre of Excellence, Faculty of Computer Systems and Software Engineering, Universiti Malaysia Pahang Lebuhraya Tun Razak, Kuantan, Pahang Darul Makmur, Malaysia.
    Optimum design of PIλDμ controller for an automatic voltage regulator system using combinatorial test design2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 11, article id e0166150Article in journal (Refereed)
    Abstract [en]

    Combinatorial test design is a plan of test that aims to reduce the amount of test cases systematically by choosing a subset of the test cases based on the combination of input variables. The subset covers all possible combinations of a given strength and hence tries to match the effectiveness of the exhaustive set. This mechanism of reduction has been used successfully in software testing research with t-way testing (where t indicates the interaction strength of combinations). Potentially, other systems may exhibit many similarities with this approach. Hence, it could form an emerging application in different areas of research due to its usefulness. To this end, more recently it has been applied in a few research areas successfully. In this paper, we explore the applicability of combinatorial test design technique for Fractional Order (FO), Proportional-Integral-Derivative (PID) parameter design controller, named as FOPID, for an automatic voltage regulator (AVR) system. Throughout the paper, we justify this new application theoretically and practically through simulations. In addition, we report on first experiments indicating its practical use in this field. We design different algorithms and adapted other strategies to cover all the combinations with an optimum and effective test set. Our findings indicate that combinatorial test design can find the combinations that lead to optimum design. Besides this, we also found that by increasing the strength of combination, we can approach to the optimum design in a way that with only 4-way combinatorial set, we can get the effectiveness of an exhaustive test set. This significantly reduced the number of tests needed and thus leads to an approach that optimizes design of parameters quickly. © 2016 Ahmed et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

  • 36. Ahmed, Saheeb
    et al.
    Wittenmayer, Nina
    Kremer, Thomas
    Hoeber, Jan
    Kiran Akula, Asha
    Urlaub, Henning
    Islinger, Markus
    Kirsch, Joachim
    Dean, Camin
    Dresbach, Thomas
    Mover is a homomeric phospho-protein present on synaptic vesicles2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 5, p. e63474-Article in journal (Refereed)
    Abstract [en]

    With remarkably few exceptions, the molecules mediating synaptic vesicle exocytosis at active zones are structurally and functionally conserved between vertebrates and invertebrates. Mover was found in a yeast-2-hybrid assay using the vertebrate-specific active zone scaffolding protein bassoon as a bait. Peptides of Mover have been reported in proteomics screens for self-interacting proteins, phosphorylated proteins, and synaptic vesicle proteins, respectively. Here, we tested the predictions arising from these screens. Using flotation assays, carbonate stripping of peripheral membrane proteins, mass spectrometry, immunogold labelling of purified synaptic vesicles, and immuno-organelle isolation, we found that Mover is indeed a peripheral synaptic vesicle membrane protein. In addition, by generating an antibody against phosphorylated Mover and Western blot analysis of fractionated rat brain, we found that Mover is a bona fide phospho-protein. The localization of Mover to synaptic vesicles is phosphorylation dependent; treatment with a phosphatase caused Mover to dissociate from synaptic vesicles. A yeast-2-hybrid screen, co-immunoprecipitation and cell-based optical assays of homomerization revealed that Mover undergoes homophilic interaction, and regions within both the N- and C- terminus of the protein are required for this interaction. Deleting a region required for homomeric interaction abolished presynaptic targeting of recombinant Mover in cultured neurons. Together, these data prove that Mover is associated with synaptic vesicles, and implicate phosphorylation and multimerization in targeting of Mover to synaptic vesicles and presynaptic sites.

  • 37.
    Ahmed, Sultan
    et al.
    Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka.
    Rekha, Rokeya Sultana
    Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka.
    Bin Ahsan, Khalid
    Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka.
    Doi, Mariko
    Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba, Japan.
    Grander, Margaretha
    Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.
    Roy, Anjan Kumar
    Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka.
    Ekström, Eva-Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Wagatsuma, Yukiko
    Department of Clinical Trial and Clinical Epidemiology, Faculty of Medicine, University of Tsukuba, Japan.
    Vahter, Marie
    Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.
    Raqib, Rubhana
    Centre for Vaccine Sciences, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka.
    Arsenic Exposure Affects Plasma Insulin-Like Growth Factor 1 (IGF-1) in Children in Rural Bangladesh2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, p. e81530-Article in journal (Refereed)
    Abstract [en]

    Background: Exposure to inorganic arsenic (As) through drinking water during pregnancy is associated with lower birth size and child growth. The aim of the study was to assess the effects of As exposure on child growth parameters to evaluate causal associations. Methodology/Findings: Children born in a longitudinal mother-child cohort in rural Bangladesh were studied at 4.5 years (n=640) as well as at birth (n=134). Exposure to arsenic was assessed by concurrent and prenatal (maternal) urinary concentrations of arsenic metabolites (U-As). Associations with plasma concentrations of insulin-like growth factor 1 (IGF-1), calcium (Ca), vitamin D (Vit-D), bone-specific alkaline phosphatase (B-ALP), intact parathyroid hormone (iPTH), and phosphate (PO4) were evaluated by linear regression analysis, adjusted for socioeconomic factor, parity and child sex. Child U-As (per 10 mu g/L) was significantly inversely associated with concurrent plasma IGF-1 (beta=-0.27; 95% confidence interval: -0.50, -0.0042) at 4.5 years. The effect was more obvious in girls (beta=-0.29; -0.59, 0.021) than in boys, and particularly in girls with adequate height (beta=-0.491; -0.97, -0.02) or weight (beta=-0.47; 0.97, 0.01). Maternal U-As was inversely associated with child IGF-1 at birth (r=-0.254, P=0.003), but not at 4.5 years. There was a tendency of positive association between U-As and plasma PO4 in stunted boys (beta=0.27; 0.089, 0.46). When stratified by % monomethylarsonic acid (MMA, arsenic metabolite) (median split at 9.7%), a much stronger inverse association between U-As and IGF-1 in the girls (beta=-0.41; -0.77, -0.03) was obtained above the median split. Conclusion: The results suggest that As-related growth impairment in children is mediated, at least partly, through suppressed IGF-1 levels.

  • 38. Aho, Vilma
    et al.
    Ollila, Hanna M.
    Rantanen, Ville
    Kronholm, Erkki
    Surakka, Ida
    van Leeuwen, Wessel M. A.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. University of Helsinki, Finland; Finnish Institute of Occupational Health, Finland.
    Lehto, Maili
    Matikainen, Sampsa
    Ripatti, Samuli
    Härmä, Mikko
    Sallinen, Mikael
    Salomaa, Veikko
    Jauhiainen, Matti
    Alenius, Harri
    Paunio, Tiina
    Porkka-Heiskanen, Tarja
    Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10, article id e77184Article in journal (Refereed)
    Abstract [en]

    Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complemented with pathway and transcription factor analysis. Expression levels of the ten most up-regulated and ten most down-regulated transcripts were correlated with subjective assessment of insufficient sleep in a population cohort (N = 472). Experimental sleep restriction altered the expression of 117 genes. Eight of the 25 most up-regulated transcripts were related to immune function. Accordingly, fifteen of the 25 most up-regulated Gene Ontology pathways were also related to immune function, including those for B cell activation, interleukin 8 production, and NF-kappa B signaling (P<0.005). Of the ten most up-regulated genes, expression of STX16 correlated negatively with self-reported insufficient sleep in a population sample, while three other genes showed tendency for positive correlation. Of the ten most down-regulated genes, TBX21 and LGR6 correlated negatively and TGFBR3 positively with insufficient sleep. Partial sleep restriction affects the regulation of signaling pathways related to the immune system. Some of these changes appear to be long-lasting and may at least partly explain how prolonged sleep restriction can contribute to inflammation-associated pathological states, such as cardiometabolic diseases.

  • 39.
    Ahooghalandari, Parvin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Hanke, Nina
    Thorpe, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Witte, Andreas
    Messinger, Josef
    Hellman, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Mutations in Arg143 and Lys192 of the Human Mast Cell Chymase Markedly Affect the Activity of Five Potent Human Chymase Inhibitors2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 6, p. e65988-Article in journal (Refereed)
    Abstract [en]

    Chymotrypsin-like serine proteases are found in high abundance in mast cell granules. By site-directed mutatgenesis, we have previously shown that basic amino acids in positions 143 and 192 (Arg and Lys respectively) of the human mast cell chymase are responsible for an acidic amino acid residue preference in the P2' position of substrates. In order to study the influence of these two residues in determining the specificity of chymase inhibitors, we have synthesized five different potent inhibitors of the human chymase. The inhibitory effects of these compounds were tested against the wild-type enzyme, against two single mutants Arg143Gln and Lys192Met and against a double mutant, Arg143Gln+Lys192Met. We observed a markedly reduced activity of all five inhibitors with the double mutant, indicating that these two basic residues are involved in conferring the specificity of these inhibitors. The single mutants showed an intermediate phenotype, with the strongest effect on the inhibitor by the mutation in Lys192. The Lys192 and the double mutations also affected the rate of cleavage of angiotensin I but did not seem to affect the specificity in the cleavage of the Tyr(4)-Ile(5) bond. A more detailed knowledge about which amino acids that confer the specificity of an enzyme can prove to be of major importance for development of highly specific inhibitors for the human chymase and other medically important enzymes.

  • 40.
    Ahs, Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Women with Multiple Chemical Sensitivity Have Increased Harm Avoidance and Reduced 5-HT1A Receptor Binding Potential in the Anterior Cingulate and Amygdala2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203Article in journal (Refereed)
    Abstract [en]

    Multiple chemical sensitivity (MCS) is a common condition, characterized by somatic distress upon exposure to odors. As in other idiopathic environmental intolerances, the underlying mechanisms are unknown. Contrary to the expectations it was recently found that persons with MCS activate the odor-processing brain regions less than controls, while their activation of the anterior cingulate cortex (ACC) is increased. The present follow-up study was designed to test the hypotheses that MCS subjects have increased harm avoidance and deviations in the serotonin system, which could render them intolerant to environmental odors. Twelve MCS and 11 control subjects, age 22–44, all working or studying females, were included in a PET study where 5-HT1A receptor binding potential (BP) was assessed after bolus injection of [11C]WAY100635. Psychological profiles were assessed by the Temperament and Character Inventory and the Swedish universities Scales of Personality. All MCS and 12 control subjects were also tested for emotional startle modulation in an acoustic startle test. MCS subjects exhibited significantly increased harm avoidance, and anxiety compared to controls. They also had a reduced 5-HT1A receptor BP in amygdala (p = 0.029), ACC (p = 0.005) (planned comparisons, significance level 0.05), and insular cortex (p = 0.003; significance level p<0.005 with Bonferroni correction), and showed an inverse correlation between degree of anxiety and the BP in the amygdala (planned comparison). No group by emotional category difference was found in the startle test. Increased harm avoidance and the observed changes in the 5-HT1A receptor BP in the regions processing harm avoidance provides a plausible pathophysiological ground for the symptoms described in MCS, and yields valuable information for our general understanding of idiopathic environmental intolerances.

  • 41.
    Akhras, Michael S.
    et al.
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Pettersson, Erik
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Diamond, Lisa
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA, USA.
    Unemo, Magnus
    Örebro University Hospital.
    Okamoto, Jennifer
    Dept Bioengn, Stanford Univ, Stanford CA, USA.; Howard Hughes Med Inst, Stanford Univ, Stanford CA, USA.
    Davis, Ronald W.
    Stanford Genome Technol Ctr, Stanford Univ, Palo Alto CA , USA.
    Pourmand, Nader
    Dept Biomol Engn, University of California, Santa Cruz CA, USA.
    The Sequencing Bead Array (SBA), a Next-Generation Digital Suspension Array2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10, article id UNSP e76696Article in journal (Refereed)
    Abstract [en]

    Here we describe the novel Sequencing Bead Array (SBA), a complete assay for molecular diagnostics and typing applications. SBA is a digital suspension array using Next-Generation Sequencing (NGS), to replace conventional optical readout platforms. The technology allows for reducing the number of instruments required in a laboratory setting, where the same NGS instrument could be employed from whole-genome and targeted sequencing to SBA broad-range biomarker detection and genotyping. As proof-of-concept, a model assay was designed that could distinguish ten Human Papillomavirus (HPV) genotypes associated with cervical cancer progression. SBA was used to genotype 20 cervical tumor samples and, when compared with amplicon pyrosequencing, was able to detect two additional co-infections due to increased sensitivity. We also introduce in-house software Sphix, enabling easy accessibility and interpretation of results. The technology offers a multi-parallel, rapid, robust, and scalable system that is readily adaptable for a multitude of microarray diagnostic and typing applications, e. g. genetic signatures, single nucleotide polymorphisms (SNPs), structural variations, and immunoassays. SBA has the potential to dramatically change the way we perform probe-based applications, and allow for a smooth transition towards the technology offered by genomic sequencing.

  • 42.
    Akhras, Michael
    et al.
    KTH, School of Biotechnology (BIO).
    Thiyagarajan, Sreedevi
    Stanford Univ, Stanford Genome Technol Ctr.
    Villablanca, Andrea C.
    Stanford Univ, Stanford Genome Technol Ctr.
    Davis, Ronald W.
    Stanford Univ, Stanford Genome Technol Ctr.
    Nyrén, Pål
    KTH, School of Biotechnology (BIO).
    Pourmand, Nader
    Stanford Univ, Stanford Genome Technol Ctr.
    PathogenMip Assay: A Multiplex Pathogen Detection Assay2007In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 2, no 2, p. e223-Article in journal (Refereed)
    Abstract [en]

    The Molecular Inversion Probe (MIP) assay has been previously applied to a large-scale human SNP detection. Here we describe the PathogenMip Assay, a complete protocol for probe production and applied approaches to pathogen detection. We have demonstrated the utility of this assay with an initial set of 24 probes targeting the most clinically relevant HPV genotypes associated with cervical cancer progression. Probe construction was based on a novel, cost-effective, ligase-based protocol. The assay was validated by performing pyrosequencing and Microarray chip detection in parallel experiments. HPV plasmids were used to validate sensitivity and selectivity of the assay. In addition, 20 genomic DNA extracts from primary tumors were genotyped with the PathogenMip Assay results and were in 100% agreement with conventional sequencing using an L1-based HPV genotyping protocol. The PathogenMip Assay is a widely accessible protocol for producing and using highly discriminating probes, with experimentally validated results in pathogen genotyping, which could potentially be applied to the detection and characterization of any microbe.

  • 43. Akhtar, Malik N.
    et al.
    Southey, Bruce R.
    Andrén, Per E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Sweedler, Jonathan V.
    Rodriguez-Zas, Sandra L.
    Accurate Assignment of Significance to Neuropeptide Identifications Using Monte Carlo K-Permuted Decoy Databases2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 10, p. e111112-Article in journal (Refereed)
    Abstract [en]

    In support of accurate neuropeptide identification in mass spectrometry experiments, novel Monte Carlo permutation testing was used to compute significance values. Testing was based on k-permuted decoy databases, where k denotes the number of permutations. These databases were integrated with a range of peptide identification indicators from three popular open-source database search software (OMSSA, Crux, and X! Tandem) to assess the statistical significance of neuropeptide spectra matches. Significance p-values were computed as the fraction of the sequences in the database with match indicator value better than or equal to the true target spectra. When applied to a test-bed of all known manually annotated mouse neuropeptides, permutation tests with k-permuted decoy databases identified up to 100% of the neuropeptides at p-value < 10(-5). The permutation test p-values using hyperscore (X! Tandem), E-value (OMSSA) and Sp score (Crux) match indicators outperformed all other match indicators. The robust performance to detect peptides of the intuitive indicator "number of matched ions between the experimental and theoretical spectra" highlights the importance of considering this indicator when the p-value was borderline significant. Our findings suggest permutation decoy databases of size 1x10(5) are adequate to accurately detect neuropeptides and this can be exploited to increase the speed of the search. The straightforward Monte Carlo permutation testing (comparable to a zero order Markov model) can be easily combined with existing peptide identification software to enable accurate and effective neuropeptide detection. The source code is available at http://stagbeetle.animal.uiuc.edu/pepshop/MSMSpermutationtesting.

  • 44.
    Akiyama, Reiko
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Ågren, Jon
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Plant Ecology and Evolution.
    Magnitude and timing of leaf damage affect seed production in a natural population of Arabidopsis thaliana (Brassicaceae)2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 1, p. e30015-Article in journal (Refereed)
    Abstract [en]

    Background: The effect of herbivory on plant fitness varies widely. Understanding the causes of this variation is of considerable interest because of its implications for plant population dynamics and trait evolution. We experimentally defoliated the annual herb Arabidopsis thaliana in a natural population in Sweden to test the hypotheses that (a) plant fitness decreases with increasing damage, (b) tolerance to defoliation is lower before flowering than during flowering, and (c) defoliation before flowering reduces number of seeds more strongly than defoliation during flowering, but the opposite is true for effects on seed size.

    Methodology/Principal Findings: In a first experiment, between 0 and 75% of the leaf area was removed in May from plants that flowered or were about to start flowering. In a second experiment, 0, 25%, or 50% of the leaf area was removed from plants on one of two occasions, in mid April when plants were either in the vegetative rosette or bolting stage, or in mid May when plants were flowering. In the first experiment, seed production was negatively related to leaf area removed, and at the highest damage level, also mean seed size was reduced. In the second experiment, removal of 50% of the leaf area reduced seed production by 60% among plants defoliated early in the season at the vegetative rosettes, and by 22% among plants defoliated early in the season at the bolting stage, but did not reduce seed output of plants defoliated one month later. No seasonal shift in the effect of defoliation on seed size was detected.

    Conclusions/Significance: The results show that leaf damage may reduce the fitness of A. thaliana, and suggest that in this population leaf herbivores feeding on plants before flowering should exert stronger selection on defence traits than those feeding on plants during flowering, given similar damage levels.

  • 45.
    Akkad, Hazem
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Corpeno Kalamgi, Rebeca
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Larsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Masseter Muscle Myofibrillar Protein Synthesis and Degradation in an Experimental Critical Illness Myopathy Model2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 4, p. e92622-Article in journal (Refereed)
    Abstract [en]

    Critical illness myopathy (CIM) is a debilitating common consequence of modern intensive care, characterized by severe muscle wasting, weakness and a decreased myosin/actin (M/A) ratio. Limb/trunk muscles are primarily affected by this myopathy while cranial nerve innervated muscles are spared or less affected, but the mechanisms underlying these muscle-specific differences remain unknown. In this time-resolved study, the cranial nerve innervated masseter muscle was studied in a unique experimental rat intensive care unit (ICU) model, where animals were exposed to sedation, neuromuscular blockade (NMB), mechanical ventilation, and immobilization for durations varying between 6 h and 14d. Gel electrophoresis, immunoblotting, RT-PCR and morphological staining techniques were used to analyze M/A ratios, myofiber size, synthesis and degradation of myofibrillar proteins, and levels of heat shock proteins (HSPs). Results obtained in the masseter muscle were compared with previous observations in experimental and clinical studies of limb muscles. Significant muscle-specific differences were observed, i.e., in the masseter, the decline in M/A ratio and muscle fiber size was small and delayed. Furthermore, transcriptional regulation of myosin and actin synthesis was maintained, and Akt phosphorylation was only briefly reduced. In studied degradation pathways, only mRNA, but not protein levels of MuRF1, atrogin-1 and the autophagy marker LC3b were activated by the ICU condition. The matrix metalloproteinase MMP-2 was inhibited and protective HSPs were up-regulated early. These results confirm that the cranial nerve innervated masticatory muscles is less affected by the ICU-stress response than limb muscles, in accordance with clinical observation in ICU patients with CIM, supporting the model' credibility as a valid CIM model.

  • 46.
    Akselsson, Anna
    et al.
    Sophiahemmet University / Karolinska Institutet.
    Lindgren, Helena
    Karolinska Institutet.
    Georgsson, Susanne
    The Swedish Red Cross University College. Karolinska Institutet.
    Pettersson, Karin
    Karolinska Institutet.
    Rådestad, Ingela
    Sophiahemmet University.
    Increased labor induction and women presenting with decreased or altered fetal movements - a population-based survey.2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 5, article id e0216216Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Women's awareness of fetal movements is important as perception of decreased fetal movements can be a sign of a compromised fetus. We aimed to study rate of labor induction in relation to number of times women seek care due to decreased or altered fetal movements during their pregnancy compared to women not seeking such care. Further, we investigated the indication of induction.

    MATERIAL AND METHODS: A prospective population-based cohort study including all obstetric clinics in Stockholm, Sweden. Questionnaires were distributed to women who sought care due to decreased or altered fetal movements ≥ 28 week's gestation in 2014, women for whom an examination did not indicate a compromised fetus that required induction of labor or cesarean section when they sought care. Women who gave birth at ≥ 28 weeks' gestation in 2014 in Stockholm comprises the reference group.

    RESULTS: Labor was induced more often among the 2683 women who had sought care due to decreased or altered fetal movements (RR 1.4, 95% CI 1.3-1.5). In women who presented with decreased or altered fetal movements induction of labor occurred more frequently for fetal indication than those with induction of labor and no prior fetal movement presentation (RR 1.6, 95% CI 1.4-1.8). The rate of induction increased with number of times a woman sought care, RR 1.3 for single presentation to 3.2 for five or more.

    CONCLUSIONS: We studied women seeking care for decreased or altered fetal movements and for whom pregnancy was not terminated with induction or caesarean section. Subsequent (median 20 days), induction of labor and induction for fetal indications were more frequent in this group compared to the group of women with no fetal movement presentations. Among women seeking care for altered or decreased fetal movements, the likelihood of induction of labor increased with frequency of presentation.

  • 47.
    Akselsson, Anna
    et al.
    Sophiahemmet University.
    Lindgren, Helena
    Georgsson, Susanne
    Pettersson, Karin
    Rådestad, Ingela
    Sophiahemmet University.
    Increased labor induction and women presenting with decreased or altered fetal movements: A population-based survey2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 5, article id e0216216Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Women's awareness of fetal movements is important as perception of decreased fetal movements can be a sign of a compromised fetus. We aimed to study rate of labor induction in relation to number of times women seek care due to decreased or altered fetal movements during their pregnancy compared to women not seeking such care. Further, we investigated the indication of induction.

    MATERIAL AND METHODS: A prospective population-based cohort study including all obstetric clinics in Stockholm, Sweden. Questionnaires were distributed to women who sought care due to decreased or altered fetal movements ≥ 28 week's gestation in 2014, women for whom an examination did not indicate a compromised fetus that required induction of labor or cesarean section when they sought care. Women who gave birth at ≥ 28 weeks' gestation in 2014 in Stockholm comprises the reference group.

    RESULTS: Labor was induced more often among the 2683 women who had sought care due to decreased or altered fetal movements (RR 1.4, 95% CI 1.3-1.5). In women who presented with decreased or altered fetal movements induction of labor occurred more frequently for fetal indication than those with induction of labor and no prior fetal movement presentation (RR 1.6, 95% CI 1.4-1.8). The rate of induction increased with number of times a woman sought care, RR 1.3 for single presentation to 3.2 for five or more.

    CONCLUSIONS: We studied women seeking care for decreased or altered fetal movements and for whom pregnancy was not terminated with induction or caesarean section. Subsequent (median 20 days), induction of labor and induction for fetal indications were more frequent in this group compared to the group of women with no fetal movement presentations. Among women seeking care for altered or decreased fetal movements, the likelihood of induction of labor increased with frequency of presentation.

  • 48.
    Akula, Srinivas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Mohammadamin, Sayran
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Hellman, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
    Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 5, p. e96903-Article in journal (Refereed)
    Abstract [en]

    Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR gamma chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

  • 49.
    Akula, Srinivas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
    Thorpe, Michael
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
    Boinapally, Vamsi
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
    Hellman, Lars
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Chemical Biology.
    Granule Associated Serine Proteases of Hematopoietic Cells - An Analysis of Their Appearance and Diversification during Vertebrate Evolution2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 11, article id e0143091Article in journal (Refereed)
    Abstract [en]

    Serine proteases are among the most abundant granule constituents of several hematopoietic cell lineages including mast cells, neutrophils, cytotoxic T cells and NK cells. These proteases are stored in their active form in the cytoplasmic granules and in mammals are encoded from four different chromosomal loci: the chymase locus, the met-ase locus, the T cell tryptase and the mast cell tryptase locus. In order to study their appearance during vertebrate evolution we have performed a bioinformatic analysis of related genes and gene loci from a large panel of metazoan animals from sea urchins to placental mammals for three of these loci: the chymase, met-ase and granzyme A/K loci. Genes related to mammalian granzymes A and K were the most well conserved and could be traced as far back to cartilaginous fish. Here, the granzyme A and K genes were found in essentially the same chromosomal location from sharks to humans. However in sharks, no genes clearly identifiable as members of the chymase or met-ase loci were found. A selection of these genes seemed to appear with bony fish, but sometimes in other loci. Genes related to mammalian met-ase locus genes were found in bony fish. Here, the most well conserved member was complement factor D. However, genes distantly related to the neutrophil proteases were also identified in this locus in several bony fish species, indicating that this locus is also old and appeared at the base of bony fish. In fish, a few of the chymase locus-related genes were found in a locus with bordering genes other than the mammalian chymase locus and some were found in the fish met-ase locus. This indicates that a convergent evolution rather than divergent evolution has resulted in chymase locus-related genes in bony fish.

  • 50.
    Al Nima, Ali
    et al.
    Department of Psychology, University of Gothenburg, Gothenburg.
    Rosenberg, Patricia
    Archer, Trevor
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science. Univ Gothenburg, Dept Psychol, S-40020 Gothenburg, Sweden.
    Garcia, Danilo
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg.
    Anxiety, Affect, Self-Esteem, and Stress: Mediation and Moderation Effects on Depression2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, p. e73265-Article in journal (Refereed)
    Abstract [en]

    Background: Mediation analysis investigates whether a variable (i.e., mediator) changes in regard to an independent variable, in turn, affecting a dependent variable. Moderation analysis, on the other hand, investigates whether the statistical interaction between independent variables predict a dependent variable. Although this difference between these two types of analysis is explicit in current literature, there is still confusion with regard to the mediating and moderating effects of different variables on depression. The purpose of this study was to assess the mediating and moderating effects of anxiety, stress, positive affect, and negative affect on depression. Methods: Two hundred and two university students (males = 93, females = 113) completed questionnaires assessing anxiety, stress, self-esteem, positive and negative affect, and depression. Mediation and moderation analyses were conducted using techniques based on standard multiple regression and hierarchical regression analyses. Main Findings: The results indicated that (i) anxiety partially mediated the effects of both stress and self-esteem upon depression, (ii) that stress partially mediated the effects of anxiety and positive affect upon depression, (iii) that stress completely mediated the effects of self-esteem on depression, and (iv) that there was a significant interaction between stress and negative affect, and between positive affect and negative affect upon depression. Conclusion: The study highlights different research questions that can be investigated depending on whether researchers decide to use the same variables as mediators and/or moderators.

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