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  • 651. Xue, Weiya
    et al.
    Ruprecht, Colin
    Street, Nathaniel
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Hematy, Kian
    Chang, Christine
    Frommer, Wolf B
    Persson, Staffan
    Niittyla, Totte
    Paramutation-like interaction of T-DNA loci in arabidopsis2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 12, s. e51651-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In paramutation, epigenetic information is transferred from one allele to another to create a gene expression state which is stably inherited over generations. Typically, paramutation describes a phenomenon where one allele of a gene down-regulates the expression of another allele. Paramutation has been described in several eukaryotes and is best understood in plants. Here we describe an unexpected paramutation-like trans SALK T-DNA interaction in Arabidopsis. Unlike most of the previously described paramutations, which led to gene silencing, the trans SALK T-DNA interaction caused an increase in the transcript levels of the endogenous gene (COBRA) where the T-DNA was inserted. This increased COBRA expression state was stably inherited for several generations and led to the partial suppression of the cobra phenotype. DNA methylation was implicated in this trans SALK T-DNA interaction since mutation of the DNA methyltransferase 1 in the suppressed cobra caused a reversal of the suppression. In addition, null mutants of the DNA demethylase ROS1 caused a similar COBRA transcript increase in the cobra SALK T-DNA mutant as the trans T-DNA interaction. Our results provide a new example of a paramutation-like trans T-DNA interaction in Arabidopsis, and establish a convenient hypocotyl elongation assay to study this phenomenon. The results also alert to the possibility of unexpected endogenous transcript increase when two T-DNAs are combined in the same genetic background. Citation: Xue W, Ruprecht C, Street N, Hematy K, Chang C, et al. (2012) Paramutation-Like Interaction of T-DNA Loci in Arabidopsis. PLoS ONE 7(12): e51651. doi:10.1371/journal.pone.0051651

  • 652. Yan, Xiaoyong
    et al.
    Minnhagen, Petter
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Maximum Entropy, Word-Frequency, Chinese Characters, and Multiple Meanings2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 5, artikel-id e0125592Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The word-frequency distribution of a text written by an author is well accounted for by a maximum entropy distribution, the RGF (random group formation)-prediction. The RGF-distribution is completely determined by the a priori values of the total number of words in the text (M), the number of distinct words (N) and the number of repetitions of the most common word (k(max)). It is here shown that this maximum entropy prediction also describes a text written in Chinese characters. In particular it is shown that although the same Chinese text written in words and Chinese characters have quite differently shaped distributions, they are nevertheless both well predicted by their respective three a priori characteristic values. It is pointed out that this is analogous to the change in the shape of the distribution when translating a given text to another language. Another consequence of the RGF-prediction is that taking a part of a long text will change the input parameters (M, N, k(max)) and consequently also the shape of the frequency distribution. This is explicitly confirmed for texts written in Chinese characters. Since the RGF-prediction has no system-specific information beyond the three a priori values (M, N, k(max)), any specific language characteristic has to be sought in systematic deviations from the RGF-prediction and the measured frequencies. One such systematic deviation is identified and, through a statistical information theoretical argument and an extended RGF-model, it is proposed that this deviation is caused by multiple meanings of Chinese characters. The effect is stronger for Chinese characters than for Chinese words. The relation between Zipf's law, the Simon-model for texts and the present results are discussed.

  • 653.
    Yanamandra, Kiran
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Alexeyev, Oleg
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Zamotin, Vladimir
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Srivastava, Vaibhav
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Shchukarev, Andrey
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Brorsson, Ann-Christin
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Tartaglia, Gian Gaetano
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Vogl, Thomas
    Institute of Immunology, University of Münster, Münster, Germany.
    Kayed, Rakez
    Department of Neurology, University of Texas Medical Branch, Galveston, Texas, United States of America.
    Wingsle, Gunnar
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Olsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Dobson, Christopher M
    Department of Chemistry, University of Cambridge, Cambridge, United Kingdom.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Elgh, Fredrik
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Morozova-Roche, Ludmilla A
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Amyloid formation by the pro-inflammatory S100A8/A9 proteins in the ageing prostate2009Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, nr 5, s. e5562-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background The conversion of soluble peptides and proteins into polymeric amyloid structures is a hallmark of many age-related degenerative disorders, including Alzheimer's disease, type II diabetes and a variety of systemic amyloidoses. We report here that amyloid formation is linked to another major age-related phenomenon - prostate tissue remodelling in middle-aged and elderly men.

    Methodology/Principal Findings By using multidisciplinary analysis of corpora amylacea inclusions in prostate glands of patients diagnosed with prostate cancer we have revealed that their major components are the amyloid forms of S100A8 and S100A9 proteins associated with numerous inflammatory conditions and types of cancer. In prostate protease rich environment the amyloids are stabilized by dystrophic calcification and lateral thickening. We have demonstrated that material closely resembling CA can be produced from S100A8/A9 in vitro under native and acidic conditions and shows the characters of amyloids. This process is facilitated by calcium or zinc, both of which are abundant in ex vivo inclusions. These observations were supported by computational analysis of the S100A8/A9 calcium-dependent aggregation propensity profiles. We found DNA and proteins from Escherichia coli in CA bodies, suggesting that their formation is likely to be associated with bacterial infection. CA inclusions were also accompanied by the activation of macrophages and by an increase in the concentration of S100A8/A9 in the surrounding tissues, indicating inflammatory reactions.

    Conclusions/Significance These findings, taken together, suggest a link between bacterial infection, inflammation and amyloid deposition of pro-inflammatory proteins S100A8/A9 in the prostate gland, such that a self-perpetuating cycle can be triggered and may increase the risk of malignancy in the ageing prostate. The results provide strong support for the prediction that the generic ability of polypeptide chains to convert into amyloids could lead to their involvement in an increasing number of otherwise apparently unrelated diseases, particularly those associated with ageing.

  • 654. Yiangou, Loukia
    et al.
    Montandon, Ruddy
    Modrzynska, Katarzyna
    Rosen, Barry
    Bushell, Wendy
    Hale, Christine
    Billker, Oliver
    Malaria Programme, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.
    Rayner, Julian C.
    Pance, Alena
    A Stem Cell Strategy Identifies Glycophorin C as a Major Erythrocyte Receptor for the Rodent Malaria Parasite Plasmodium berghei2016Ingår i: PLoS ONE, E-ISSN 1932-6203, Vol. 11, nr 6, artikel-id e0158238Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The clinical complications of malaria are caused by the parasite expansion in the blood. Invasion of erythrocytes is a complex process that depends on multiple receptor-ligand interactions. Identification of host receptors is paramount for fighting the disease as it could reveal new intervention targets, but the enucleated nature of erythrocytes makes genetic approaches impossible and many receptors remain unknown. Host-parasite interactions evolve rapidly and are therefore likely to be species-specific. As a results, understanding of invasion receptors outside the major human pathogen Plasmodium falciparum is very limited. Here we use mouse embryonic stem cells (mESCs) that can be genetically engineered and differentiated into erythrocytes to identify receptors for the rodent malaria parasite Plasmodium berghei. Two proteins previously implicated in human malaria infection: glycophorin C (GYPC) and Band-3 (Slc4a1) were deleted in mESCs to generate stable cell lines, which were differentiated towards erythropoiesis. In vitro infection assays revealed that while deletion of Band-3 has no effect, absence of GYPC results in a dramatic decrease in invasion, demonstrating the crucial role of this protein for P. berghei infection. This stem cell approach offers the possibility of targeting genes that may be essential and therefore difficult to disrupt in whole organisms and has the potential to be applied to a variety of parasites in diverse host cell types.

  • 655.
    Yu, Ji-Guo
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Bonnerud, Patrik
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Eriksson, Anders
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Stål, Per S.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Tegner, Yelverton
    Department of Health Sciences, Luleå University of Technology, Luleå.
    Malm, Christer
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Effects of long term supplementation of anabolic androgen steroids on human skeletal muscle2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 9, artikel-id e105330Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The effects of long-term (over several years) anabolic androgen steroids (AAS) administration on human skeletal muscle are still unclear. In this study, seventeen strength training athletes were recruited and individually interviewed regarding self-administration of banned substances. Ten subjects admitted having taken AAS or AAS derivatives for the past 5 to 15 years (Doped) and the dosage and type of banned substances were recorded. The remaining seven subjects testified to having never used any banned substances (Clean). For all subjects, maximal muscle strength and body composition were tested, and biopsies from the vastus lateralis muscle were obtained. Using histochemistry and immunohistochemistry (IHC), muscle biopsies were evaluated for morphology including fiber type composition, fiber size, capillary variables and myonuclei. Compared with the Clean athletes, the Doped athletes had significantly higher lean leg mass, capillary per fibre and myonuclei per fiber. In contrast, the Doped athletes had significantly lower absolute value in maximal squat force and relative values in maximal squat force (relative to lean body mass, to lean leg mass and to muscle fiber area). Using multivariate statistics, an orthogonal projection of latent structure discriminant analysis (OPLS-DA) model was established, in which the maximal squat force relative to muscle mass and the maximal squat force relative to fiber area, together with capillary density and nuclei density were the most important variables for separating Doped from the Clean athletes (regression  =  0.93 and prediction  =  0.92, p<0.0001). In Doped athletes, AAS dose-dependent increases were observed in lean body mass, muscle fiber area, capillary density and myonuclei density. In conclusion, long term AAS supplementation led to increases in lean leg mass, muscle fiber size and a parallel improvement in muscle strength, and all were dose-dependent. Administration of AAS may induce sustained morphological changes in human skeletal muscle, leading to physical performance enhancement.

  • 656.
    Yu, Ji-Guo
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Idrottsmedicin.
    Liu, Jing-Xia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Carlsson, Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Thornell, Lars-Eric
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Stål, Per S
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Anatomi.
    Re-evaluation of sarcolemma injury and muscle swelling in human skeletal muscles after eccentric exercise2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 4, artikel-id e62056Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The results regarding the effects of unaccustomed eccentric exercise on muscle tissue are often conflicting and the aetiology of delayed onset muscle soreness (DOMS) induced by eccentric exercise is still unclear. This study aimed to re-evaluate the paradigm of muscular alterations with regard to muscle sarcolemma integrity and fibre swelling in human muscles after voluntary eccentric exercise leading to DOMS. Ten young males performed eccentric exercise by downstairs running. Biopsies from the soleus muscle were obtained from 6 non-exercising controls, 4 exercised subjects within 1 hour and 6 exercised subjects at 2-3 days and 7-8 days after the exercise. Muscle fibre sarcolemma integrity, infiltration of inflammatory cells and changes in fibre size and fibre phenotype composition as well as capillary supply were examined with specific antibodies using enzyme histochemistry and immunohistochemistry. Although all exercised subjects experienced DOMS which peaked between 1.5 to 2.5 days post exercise, no significant sarcolemma injury or inflammation was detected in any post exercise group. The results do not support the prevailing hypothesis that eccentric exercise causes an initial sarcolemma injury which leads to subsequent inflammation after eccentric exercise. The fibre size was 24% larger at 7-8 days than at 2-3 days post exercise (p<0.05). In contrast, the value of capillary number per fibre area tended to decrease from 2-3 days to 7-8 days post exercise (lower in 5 of the 6 subjects at 7-8 days than at 2-3 days; p<0.05). Thus, the increased fibre size at 7-8 days post exercise was interpreted to reflect fibre swelling. Because the fibre swelling did not appear at the time that DOMS peaked (between 1.5 to 2.5 days post exercise), we concluded that fibre swelling in the soleus muscle is not directly associated with the symptom of DOMS.

  • 657. Zaki, Rafdzah
    et al.
    Roffeei, Siti Norsyuhada
    Hii, Yien Ling
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Yahya, Abqariyah
    Appannan, Mahesh
    Said, Mas Ayu
    Wan, Ng Chiu
    Aghamohammadi, Nasrin
    Hairi, Noran Naqiah
    Bulgiba, Awang
    Quam, Mikkel Brandon
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Rocklöv, Joacim
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Public perception and attitude towards dengue prevention activity and response to dengue early warning in Malaysia2019Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, nr 2, artikel-id e0212497Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An early warning system for dengue is meant to predict outbreaks and prevent dengue cases by aiding timely decision making and deployment of interventions. However, only a system which is accepted and utilised by the public would be sustainable in the long run. This study aimed to explore the perception and attitude of the Malaysian public towards a dengue early warning system. The sample consisted of 847 individuals who were 18 years and above and living/working in the Petaling District, an area adjacent to Kuala Lumpur, Malaysia. A questionnaire consisting of personal information and three sub-measures of; i) perception, ii) attitude towards dengue early warning and iii) response towards early warning; was distributed to participants. We found that most of the respondents know about dengue fever (97.1%) and its association with climate factors (90.6%). Most of them wanted to help reduce the number of dengue cases in their area (91.5%). A small percentage of the respondents admitted that they were not willing to be involved in public activities, and 64% of them admitted that they did not check dengue situations or hotspots around their area regularly. Despite the high awareness on the relationship between climate and dengue, about 45% of respondents do not know or are not sure how this can be used to predict dengue. Respondents would like to know more about how climate data can be used to predict a dengue outbreak (92.7%). Providing more information on how climate can influence dengue cases would increase public acceptability and improve response towards climate-based warning system. The most preferred way of communicating early warning was through the television (66.4%). This study shows that the public in Petaling District considers it necessary to have a dengue warning system to be necessary, but more education is required.

  • 658.
    Zetterström, Caroline E.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    Hasselgren, Jenny
    Creative Antibiotics Sweden AB, Umeå, Sweden .
    Salin, Olli
    Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Davis, Rohan A.
    Eskitis Institute, Griffith University, Brisbane, Australia.
    Quinn, Ronald J.
    Eskitis Institute, Griffith University, Brisbane, Australia.
    Sundin, Charlotta
    Creative Antibiotics Sweden AB, Umeå, Sweden .
    Elofsson, Mikael
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    The Resveratrol Tetramer (-)-Hopeaphenol Inhibits Type III Secretion in the Gram-Negative Pathogens Yersinia pseudotuberculosis and Pseudomonas aeruginosa2013Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, nr 12, artikel-id e81969Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Society faces huge challenges, as a large number of bacteria have developed resistance towards many or all of the antibiotics currently available. Novel strategies that can help solve this problem are urgently needed. One such strategy is to target bacterial virulence, the ability to cause disease e.g., by inhibition of type III secretion systems (T3SSs) utilized by many clinically relevant gram-negative pathogens. Many of the antibiotics used today originate from natural sources. In contrast, most virulence-blocking compounds towards the T3SS identified so far are small organic molecules. A recent high-throughput screening of a prefractionated natural product library identified the resveratrol tetramer (-)-hopeaphenol as an inhibitor of the T3SS in Yersinia pseudotuberculosis. In this study we have investigated the virulence blocking properties of (-)-hopeaphenol in three different gram-negative bacteria. (-)- Hopeaphenol was found to have micromolar activity towards the T3SSs in Yersinia pseudotuberculosis and Pseudomonas aeruginosa in cell-based infection models. In addition (-)-hopeaphenol reduced cell entry and subsequent intracellular growth of Chlamydia trachomatis.

  • 659.
    Zhang, Ce
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Liu, Yonggang
    Gilthorpe, Jonathan
    Umeå universitet, Medicinska fakulteten, Umeå centrum för molekylär medicin (UCMM).
    van der Maarel, Johan RC
    MRP14 (S100A9) protein interacts with alzheimer beta-amyloid peptide and induces its fibrillization2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 3, s. e32953-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Increasing evidence supports the contribution of local inflammation to the development of Alzheimer's disease (AD) pathology, although the precise mechanisms are not clear. In this study, we demonstrate that the pro-inflammatory protein S100A9 interacts with the A beta 1-40 peptide and promotes the formation of fibrillar beta-amyloid structures. This interaction also results in reduced S100A9 cytotoxicity by the binding of S100A9 toxic species to A beta 1-40 amyloid structures. These results suggest that secretion of S100A9 during inflammation promotes the formation of amyloid plaques. By acting as a sink for toxic species, plaque formation may be the result of a protective response within the brain of AD patients, in part mediated by S100A9.

  • 660. Zhang, Lifang
    et al.
    Selao, Tiago Toscano
    Selstam, Eva
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Norling, Birgitta
    Subcellular Localization of Carotenoid Biosynthesis in Synechocystis sp PCC 68032015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 6, artikel-id e0130904Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The biosynthesis pathway of carotenoids in cyanobacteria is partly described. However, the subcellular localization of individual steps is so far unknown. Carotenoid analysis of different membrane subfractions in Synechocystis sp. PCC6803 shows that "light" plasma membranes have a high carotenoid/protein ratio, when compared to "heavier" plasma membranes or thylakoids. The localization of CrtQ and CrtO, two well-defined carotenoid synthesis pathway enzymes in Synechocystis, was studied by epitope tagging and western blots. Both enzymes are locally more abundant in plasma membranes than in thylakoids, implying that the plasma membrane has higher synthesis rates of beta-carotene precursor molecules and echinenone.

  • 661. Zhao, Charlie W.
    et al.
    Daley, Mark J.
    Pruszynski, J. Andrew
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Dept. of Computer Science, Western University, London, Ontario, Canada; Brain and Mind Institute, Western University, London, Ontario, Canada; Dept. of Physiology and Pharmacology, Western University, London, Ontario, Canada; Dept. of Psychology, Western University, London, Ontario, Canada; Robarts Research Institute, Western University, London, Ontario, Canada.
    Neural network models of the tactile system develop first-order units with spatially complex receptive fields2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 6, artikel-id e0199196Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    First-order tactile neurons have spatially complex receptive fields. Here we use machine-learning tools to show that such complexity arises for a wide range of training sets and network architectures. Moreover, we demonstrate that this complexity benefits network performance, especially on more difficult tasks and in the presence of noise. Our work suggests that spatially complex receptive fields are normatively good given the biological constraints of the tactile periphery.

  • 662.
    Zhao, Jing
    et al.
    Department of Mathematics, Logistical Engineering University, Chongqing, China.
    Yang, Ting-Hong
    Department of Mathematics, Logistical Engineering University, Chongqing, China.
    Huang, Yongxu
    Department of Health Policy & Management, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
    Holme, Petter
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Ranking candidate disease genes from gene expression and protein interaction: a katz-centrality based approach2011Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, nr 9, s. e24306-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Many diseases have complex genetic causes, where a set of alleles can affect the propensity of getting the disease. The identification of such disease genes is important to understand the mechanistic and evolutionary aspects of pathogenesis, improve diagnosis and treatment of the disease, and aid in drug discovery. Current genetic studies typically identify chromosomal regions associated specific diseases. But picking out an unknown disease gene from hundreds of candidates located on the same genomic interval is still challenging. In this study, we propose an approach to prioritize candidate genes by integrating data of gene expression level, protein-protein interaction strength and known disease genes. Our method is based only on two, simple, biologically motivated assumptions—that a gene is a good disease-gene candidate if it is differentially expressed in cases and controls, or that it is close to other disease-gene candidates in its protein interaction network. We tested our method on 40 diseases in 58 gene expression datasets of the NCBI Gene Expression Omnibus database. On these datasets our method is able to predict unknown disease genes as well as identifying pleiotropic genes involved in the physiological cellular processes of many diseases. Our study not only provides an effective algorithm for prioritizing candidate disease genes but is also a way to discover phenotypic interdependency, cooccurrence and shared pathophysiology between different disorders.

  • 663. Zijnge, Vincent
    et al.
    Kieselbach, Thomas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Oscarsson, Jan
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral mikrobiologi.
    Proteomics of protein secretion by aggregatibacter actinomycetemcomitans2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 7, s. e41662-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The extracellular proteome (secretome) of periodontitis-associated bacteria may constitute a major link between periodontitis and systemic diseases. To obtain an overview of the virulence potential of Aggregatibacter actinomycetemcomitans, an oral and systemic human pathogen implicated in aggressive periodontitis, we used a combined LC-MS/MS and bioinformatics approach to characterize the secretome and protein secretion pathways of the rough-colony serotype a strain D7S. LC-MS/MS revealed 179 proteins secreted during biofilm growth. Further to confirming the release of established virulence factors (e.g. cytolethal distending toxin [CDT], and leukotoxin [LtxA]), we identified additional putative virulence determinants in the secretome. These included DegQ, fHbp, LppC, Macrophage infectivity protein (MIP), NlpB, Pcp, PotD, TolB, and TolC. This finding indicates that the number of extracellular virulence-related proteins is much larger than previously demonstrated, which was also supported by in silico analysis of the strain D7S genome. Moreover, our LC-MS/MS and in silico data revealed that at least Type I, II, and V secretion are actively used to excrete proteins directly into the extracellular space, or via two-step pathways involving the Sec/Tat systems for transport across the inner membrane, and outer membrane factors, secretins and auto-transporters, respectively for delivery across the outer membrane. Taken together, our results provide a molecular basis for further elucidating the role of A. actinomycetemcomitans in periodontal and systemic diseases.

  • 664.
    Ångström-Brännström, Charlotte
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Engvall, Gunn
    Mullaney, Tara
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Designhögskolan vid Umeå universitet.
    Nilsson, Kristina
    Wickart-Johansson, Gun
    Svärd, Anna-Maja
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Nyholm, Tufve
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Lindh, Jack
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Lindh, Viveca
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Children Undergoing Radiotherapy: Swedish Parents' Experiences and Suggestions for Improvement2015Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 10, artikel-id e0141086Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Approximately 300 children, from 0 to 18 years old, are diagnosed with cancer in Sweden every year. Of these children, 80-90 of them undergo radiotherapy treatment for their cancer. Although radiotherapy is an encounter with advanced technology, few studies have investigated the child's and the parent's view of the procedure. As part of an ongoing multi-center study aimed to improve patient preparation and the care environment in pediatric radiotherapy, this article reports the findings from interviews with parents at baseline. The aim of the present study was twofold: to describe parents' experience when their child undergoes radiotherapy treatment, and to report parents' suggestions for improvements during radiotherapy for their children. Sixteen mothers and sixteen fathers of children between 2-16 years old with various cancer diagnoses were interviewed. Data were analyzed using content analysis. The findings showed that cancer and treatment turns people's lives upside down, affecting the entire family. Further, the parents experience the child's suffering and must cope with intense feelings. Radiotherapy treatment includes preparation by skilled and empathetic staff. The parents gradually find that they can deal with the process; and lastly, parents have suggestions for improvements during the radiotherapy treatment. An overarching theme emerged: that despair gradually turns to a sense of security, with a sustained focus on and close interaction with the child. In conclusion, an extreme burden was experienced around the start of radiotherapy, though parents gradually coped with the process.

  • 665.
    Ögren, Joachim
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Irewall, Anna-Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Söderström, Lars
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Serious hemorrhages after ischemic stroke or TIA - Incidence, mortality, and predictors2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 4, artikel-id e0195324Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Data are lacking on the risk and impact of a serious hemorrhage on the prognosis after ischemic stroke (IS) or transient ischemic attack (TIA). We aimed to estimate the incidence of serious hemorrhage, analyze the impact on mortality, and identify predictors of hemorrhage after discharge from IS or TIA.

    Methods and findings: All patients admitted to Östersund Hospital for an IS or TIA in 2010–2013 were included (n = 1528, mean age: 75.1 years). Serious hemorrhages were identified until 31st December 2015. Incidence rates were calculated. The impact on mortality (stratified by functional level) was determined with Kaplan-Meier analysis. Non-parametric estimation under the assumption of competing risk was performed to assess the cumulative incidence and predictors of serious hemorrhages. The incidence rates of serious (n = 113) and intracranial hemorrhages (n = 45) after discharge from IS and TIA were 2.48% and 0.96% per year at risk, respectively. Patients with modified Rankin Scale (mRS) scores of 3–5 exhibited 58.9% mortality during follow-up and those with mRS scores of 0–2 exhibited 18.4% mortality. A serious hemorrhage did not affect mortality in patients with impaired functional status, but it increased the risk of death in patients with mRS scores of 0–2. Hypertension was associated with increased risk of serious hemorrhage.

    Conclusions: We found that, after discharge from an IS or TIA, serious hemorrhages were fairly common. Impairments in function were associated with high mortality, but serious hemorrhages only increased the risk of mortality in patients with no or slight disability. Improved hypertension treatment may decrease the risk of serious hemorrhage, but in patients with low functional status, poor survival makes secondary prevention challenging.

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