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  • 1.
    Abdullah Nasir, Ahmad
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Herdenberg, Carl
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Hedman, Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Oncology Research Laboratory, NUS M31, Umeå, Sweden.
    Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling2021Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 8585Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Netrin-1 is a secreted protein that is well known for its involvement in axonal guidance during embryonic development and as an enhancer of cancer cell metastasis. Despite extensive efforts, the molecular mechanisms behind many of the physiological functions of netrin-1 have remained elusive. Here, we show that netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling in various cellular systems, including a mutually inhibitory interaction with the BMP-promoting function of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins. The BMP inhibitory function of netrin-1 in mouse embryonic fibroblasts was dependent on the netrin receptor neogenin, with the expression level regulated by both netrin-1 and LRIG proteins. Our results reveal a previously unrecognized function of netrin-1 that may help to explain several of the developmental, physiological, and cancer-promoting functions of netrins at the signal transduction level.

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  • 2. Abzhandadze, Tamar
    et al.
    Reinholdsson, Malin
    Palstam, Annie
    Eriksson, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Sunnerhagen, Katharina S.
    Transforming self-reported outcomes from a stroke register to the modified Rankin Scale: a cross-sectional, explorative study2020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 17215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim was to create an algorithm to transform self-reported outcomes from a stroke register to the modified Rankin Scale (mRS). Two stroke registers were used: the Väststroke, a local register in Gothenburg, Sweden, and the Riksstroke, a Swedish national register. The reference variable, mRS (from Väststroke), was mapped with seven self-reported questions from Riksstroke. The transformation algorithm was created as a result of manual mapping performed by healthcare professionals. A supervised machine learning method—decision tree—was used to further evaluate the transformation algorithm. Of 1145 patients, 54% were male, the mean age was 71 y. The mRS grades 0, 1 and 2 could not be distinguished as a result of manual mapping or by using the decision tree analysis. Thus, these grades were merged. With manual mapping, 78% of the patients were correctly classified, and the level of agreement was almost perfect, weighted Kappa (Kw) was 0.81. With the decision tree, 80% of the patients were correctly classified, and substantial agreement was achieved, Kw = 0.67. The self-reported outcomes from a stroke register can be transformed to the mRS. A mRS algorithm based on manual mapping might be useful for researchers using self-reported questionnaire data.

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  • 3.
    Ahlinder, Jon
    et al.
    Division of CBRN Defence and Security, Swedish Defence Research Agency, Umeå, Sweden.
    Giles, Barbara
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    García-Gil, M. Rosario
    Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Life stage-specific inbreeding depression in long-lived Pinaceae species depends on population connectivity2021Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 8834Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Inbreeding depression (ID) is a fundamental selective pressure that shapes mating systems and population genetic structures in plants. Although it has been shown that ID varies over the life stages of shorter-lived plants, less is known about how the fitness effects of inbreeding vary across life stages in long-lived species. We conducted a literature survey in the Pinaceae, a tree family known to harbour some of the highest mutational loads ever reported. Using a meta-regression model, we investigated distributions of inbreeding depression over life stages, adjusting for effects of inbreeding levels and the genetic differentiation of populations within species. The final dataset contained 147 estimates of ID across life stages from 41 studies. 44 Fst estimates were collected from 40 peer-reviewed studies for the 18 species to aid genetic differentiation modelling. Partitioning species into fragmented and well-connected groups using Fst resulted in the best way (i.e. trade-off between high goodness-of-fit of the model to the data and reduced model complexity) to incorporate genetic connectivity in the meta-regression analysis. Inclusion of a life stage term and its interaction with the inbreeding coefficient (F) dramatically increased model precision. We observed that the correlation between ID and F was significant at the earliest life stage. Although partitioning of species populations into fragmented and well-connected groups explained little of the between-study heterogeneity, the inclusion of an interaction between life stage and population differentiation revealed that populations with fragmented distributions suffered lower inbreeding depression at early embryonic stages than species with well-connected populations. There was no evidence for increased ID in late life stages in well-connected populations, although ID tended to increase across life stages in the fragmented group. These findings suggest that life stage data should be included in inbreeding depression studies and that inbreeding needs to be managed over life stages in commercial populations of long-lived plants.

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  • 4. Ahlqvist, Viktor H.
    et al.
    Persson, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Ortega, Francisco B.
    Tynelius, Per
    Magnusson, Cecilia
    Berglind, Daniel
    Birth weight and grip strength in young Swedish males: a longitudinal matched sibling analysis and across all body mass index ranges2019Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 9, artikel-id 9719Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Low birth weight is associated with a lower grip strength later in life. However, associations between birth weight among infants born at-term and factors driving associations between birth weight and grip strength are largely unknown. A cohort of 144,369 young men born at-term, including 10,791 individuals who had at least one male sibling/s, were followed until conscription where they performed a grip strength test. We used linear and non-linear regression analyses in the full cohort, and fixed-effects regression analyses in the sibling cohort, to address confounding by factors that are shared between siblings. After adjustment, each unit increase in birth weight z-score was associated with increases of 17.7 (95% CI, 17.2-18.2) and 13.4 (10.1-16.6) newton grip strength, which converts to approximately 1.8 and 1.4 kilogram-force in the full and within-families cohorts, respectively. The associations did not vary with young adulthood BMI. Birth weight, within the at-term range, is robustly positively associated with grip strength in young adulthood among men across all BMI categories and associations appears to be mainly driven by factors that are not shared between siblings. These findings underline the importance of recognizing the influence of low birth weight, also within the at-termrange, on young adulthood muscle strength.

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  • 5.
    Ahmad, Irfan
    et al.
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan.
    Nygren, Evelina
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Khalid, Fizza
    Myint, Si Lhyam
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Uhlin, Bernt Eric
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    A Cyclic-di-GMP signalling network regulates biofilm formation and surface associated motility of Acinetobacter baumannii 179782020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 1991Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Acinetobacter baumannii has emerged as an increasing multidrug-resistant threat in hospitals and a common opportunistic nosocomial pathogen worldwide. However, molecular details of the pathogenesis and physiology of this bacterium largely remain to be elucidated. Here we identify and characterize the c-di-GMP signalling network and assess its role in biofilm formation and surface associated motility. Bioinformatic analysis revealed eleven candidate genes for c-di-GMP metabolizing proteins (GGDEF/EAL domain proteins) in the genome of A. baumannii strain 17978. Enzymatic activity of the encoded proteins was assessed by molecular cloning and expression in the model organisms Salmonella typhimurium and Vibrio cholerae. Ten of the eleven GGDEF/EAL proteins altered the rdar morphotype of S. typhimurium and the rugose morphotype of V. cholerae. The over expression of three GGDEF proteins exerted a pronounced effect on colony formation of A. baumannii on Congo Red agar plates. Distinct panels of GGDEF/EAL proteins were found to alter biofilm formation and surface associated motility of A. baumannii upon over expression. The GGDEF protein A1S_3296 appeared as a major diguanylate cyclase regulating macro-colony formation, biofilm formation and the surface associated motility. AIS_3296 promotes Csu pili mediated biofilm formation. We conclude that a functional c-di-GMP signalling network in A. baumannii regulates biofilm formation and surface associated motility of this increasingly important opportunistic bacterial pathogen.

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  • 6. Akkaya, Munir
    et al.
    Bansal, Abhisheka
    Sheehan, Patrick W.
    Pena, Mirna
    Cimperman, Clare K.
    Qi, Chen Feng
    Yazew, Takele
    Otto, Thomas D.
    Billker, Oliver
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Miller, Louis H.
    Pierce, Susan K.
    Testing the impact of a single nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor on experimental cerebral malaria in mice2020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 13630Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cerebral malaria (CM) is the deadliest form of severe Plasmodium infections. Currently, we have limited understanding of the mechanisms by which Plasmodium parasites induce CM. The mouse model of CM, experimental CM (ECM), induced by infection with the rodent parasite, Plasmodium berghei ANKA (PbANKA) has been extensively used to study the pathophysiology of CM. Recent genomic analyses revealed that the coding regions of PbANKA and the closely related Plasmodium berghei NK65 (PbNK65), that does not cause ECM, differ in only 21 single nucleotide polymorphysims (SNPs). Thus, the SNP-containing genes might contribute to the pathogenesis of ECM. Although the majority of these SNPs are located in genes of unknown function, one SNP is located in the DNA binding site of a member of the Plasmodium ApiAP2 transcription factor family, that we recently showed functions as a virulence factor alternating the host's immune response to the parasite. Here, we investigated the impact of this SNP on the development of ECM. Our results using CRISPR-Cas9 engineered parasites indicate that despite its immune modulatory function, the SNP is neither necessary nor sufficient to induce ECM and thus cannot account for parasite strain-specific differences in ECM phenotypes.

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  • 7.
    Alakpa, Enateri V.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Jayawarna, Vineetha
    Burgess, Karl E. V.
    West, Christopher C.
    Peault, Bruno
    Ulijn, Rein V.
    Dalby, Matthew J.
    Improving cartilage phenotype from differentiated pericytes in tunable peptide hydrogels2017Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 7, artikel-id 6895Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Differentiation of stem cells to chondrocytes in vitro usually results in a heterogeneous phenotype. This is evident in the often detected over expression of type X collagen which, in hyaline cartilage structure is not characteristic of the mid-zone but of the deep-zone ossifying tissue. Methods to better match cartilage developed in vitro to characteristic in vivo features are therefore highly desirable in regenerative medicine. This study compares phenotype characteristics between pericytes, obtained from human adipose tissue, differentiated using diphenylalanine/serine (F2/S) peptide hydrogels with the more widely used chemical induced method for chondrogenesis. Significantly higher levels of type II collagen were noted when pericytes undergo chondrogenesis in the hydrogel in the absence of induction media. There is also a balanced expression of collagen relative to aggrecan production, a feature which was biased toward collagen production when cells were cultured with induction media. Lastly, metabolic profiles of each system show considerable overlap between both differentiation methods but subtle differences which potentially give rise to their resultant phenotype can be ascertained. The study highlights how material and chemical alterations in the cellular microenvironment have wide ranging effects on resultant tissue type.

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  • 8.
    Alam, Athar
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Golovliov, Igor
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Javed, Eram
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    ClpB mutants of Francisella tularensis subspecies holarctica and tularensis are defective for type VI secretion and intracellular replication2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 11324Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Francisella tularensis, a highly infectious, intracellular bacterium possesses an atypical type VI secretion system (T6SS), which is essential for the virulence of the bacterium. Recent data suggest that the HSP100 family member, ClpB, is involved in T6SS disassembly in the subspecies Francisella novicida. Here, we investigated the role of ClpB for the function of the T6SS and for phenotypic characteristics of the human pathogenic subspecies holarctica and tularensis. The Delta clpB mutants of the human live vaccine strain, LVS, belonging to subspecies holarctica, and the highly virulent SCHU S4 strain, belonging to subspecies tularensis, both showed extreme susceptibility to heat shock and low pH, severely impaired type VI secretion (T6S), and significant, but impaired intracellular replication compared to the wild-type strains. Moreover, they showed essentially intact phagosomal escape. Infection of mice demonstrated that both Delta clpB mutants were highly attenuated, but the SCHU S4 mutant showed more effective replication than the LVS strain. Collectively, our data demonstrate that ClpB performs multiple functions in the F. tularensis subspecies holarctica and tularensis and its function is important for T6S, intracellular replication, and virulence.

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  • 9. Alaridah, Nader
    et al.
    Hallbäck, Erika Tång
    Tångrot, Jeanette
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). National Bioinformatics Infrastructure Sweden (NBIS), SciLifeLab, Computational Life Science Cluster, Umeå University, Umeå, Sweden.
    Winqvistz, Niclas
    Sturegard, Erik
    Floren-Johanssons, Kerstin
    Jonsson, Bodil
    Tenland, Erik
    Welinder-Olssons, Christina
    Medstrand, Patrik
    Kaijser, Bertil
    Godaly, Gabriela
    Transmission dynamics study of tuberculosis isolates with whole genome sequencing in southern Sweden2019Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 9, artikel-id 4931Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Epidemiological contact tracing complemented with genotyping of clinical Mycobacterium tuberculosis isolates is important for understanding disease transmission. In Sweden, tuberculosis (TB) is mostly reported in migrant and homeless where epidemiologic contact tracing could pose a problem. This study compared epidemiologic linking with genotyping in a low burden country. Mycobacterium tuberculosis isolates (n = 93) collected at Scania University Hospital in Southern Sweden were analysed with the standard genotyping method mycobacterial interspersed repetitive units-variable number tandem repeats (MIRU-VNTR) and the results were compared with whole genome sequencing (WGS). Using a maximum of twelve single nucleotide polymorphisms (SNPs) as the upper threshold of genomic relatedness noted among hosts, we identified 18 clusters with WGS comprising 52 patients with overall pairwise genetic maximum distances ranging from zero to nine SNPs. MIRU-VNTR and WGS clustered the same isolates, although the distribution differed depending on MIRU-VNTR limitations. Both genotyping techniques identified clusters where epidemiologic linking was insufficient, although WGS had higher correlation with epidemiologic data. To summarize, WGS provided better resolution of transmission than MIRU-VNTR in a setting with low TB incidence. WGS predicted epidemiologic links better which could consolidate and correct the epidemiologically linked cases, avoiding thus false clustering.

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  • 10.
    Alegria Zufia, Javier
    et al.
    Department of Biology and Environmental Science, Centre for Ecology and Evolution in Microbial Model Systems (EEMiS), Linnaeus University, Kalmar, Sweden.
    Legrand, Catherine
    Farnelid, Hanna
    Seasonal dynamics in picocyanobacterial abundance and clade composition at coastal and offshore stations in the Baltic Sea2022Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, nr 1, artikel-id 14330Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Picocyanobacteria (< 2 um in diameter) are significant contributors to total phytoplankton biomass. Due to the high diversity within this group, their seasonal dynamics and relationship with environmental parameters, especially in brackish waters, are largely unknown. In this study, the abundance and community composition of phycoerythrin rich picocyanobacteria (PE-SYN) and phycocyanin rich picocyanobacteria (PC-SYN) were monitored at a coastal (K-station) and at an offshore station (LMO; similar to 10 km from land) in the Baltic Sea over three years (2018-2020). Cell abundances of picocyanobacteria correlated positively to temperature and negatively to nitrate (NO3) concentration. While PE-SYN abundance correlated to the presence of nitrogen fixers, PC-SYN abundance was linked to stratification/shallow waters. The picocyanobacterial targeted amplicon sequencing revealed an unprecedented diversity of 2169 picocyanobacterial amplicons sequence variants (ASVs). A unique assemblage of distinct picocyanobacterial clades across seasons was identified. Clade A/B dominated the picocyanobacterial community, except during summer when low NO3, high phosphate (PO4) concentrations and warm temperatures promoted S5.2 dominance. This study, providing multiyear data, links picocyanobacterial populations to environmental parameters. The difference in the response of the two functional groups and clades underscore the need for further high-resolution studies to understand their role in the ecosystem.

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  • 11.
    Alhouayek, Mireille
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Sorti, René
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Gilthorpe, Jonathan D.
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Fowler, Christopher J
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
    Role of pannexin-1 in the cellular uptake, release and hydrolysis of anandamide by T84 colon cancer cells2019Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 9, artikel-id 7622Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The large pore ion channel pannexin-1 (Panx1) has been reported to play a role in the cellular uptake and release of anandamide (AEA) in the hippocampus. It is not known whether this is a general mechanism or limited to the hippocampus. We have investigated this pharmacologically using T84 colon cancer cells. The cells expressed Panx1 at the mRNA level, and released ATP in a manner that could be reduced by treatment with the Panx1 inhibitors carbenoxolone and mefloquine and the Panxl substrate SR101. However, no significant effects of these compounds upon the uptake or hydrolysis of exogenously applied AEA was seen. Uptake by T84 cells of the other main endocannabinoid 2-arachidonoylglycerol and the AEA homologue palmitoylethanolamide was similarly not affected by carbenoxolone or mefloquine. Total release of tritium from [H-3]AEA-prelabelled T84 cells over 10 min was increased, rather than inhibited by carbenoxolone and mefloquine. Finally, AEA uptake by PC3 prostate cancer and SH-SY5Y neuroblastoma cells, which express functional Panx1 channels, was not inhibited by carbenoxolone. Thus, in contrast to the hippocampus, Panx1 does not appear to play a role in AEA uptake and release from the cells studied under the conditions used.

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  • 12.
    Alhouayek, Mireille
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Stafberg, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Karlsson, Jessica
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Halin Bergström, Sofia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Fowler, Christopher J
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Effects of orthotopic implantation of rat prostate tumour cells upon components of the N-acylethanolamine and monoacylglycerol signalling systems: an mRNA study2020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 6314Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is good evidence that the N-acylethanolamine (NAE)/monoacylglycerol (MAG) signalling systems are involved in the pathogenesis of cancer. However, it is not known how prostate tumours affect these systems in the surrounding non-malignant tissue and vice versa. In the present study we have investigated at the mRNA level 11 components of these systems (three coding for anabolic enzymes, two for NAE/MAG targets and six coding for catabolic enzymes) in rat prostate tissue following orthotopic injection of low metastatic AT1 cells and high metastatic MLL cells. The MLL tumours expressed higher levels of Napepld, coding for a key enzyme in NAE synthesis, and lower levels of Naaa, coding for the NAE hydrolytic enzyme N-acylethanolamine acid amide hydrolase than the AT1 tumours. mRNA levels of the components of the NAE/MAG signalling systems studied in the tissue surrounding the tumours were not overtly affected by the tumours. AT1 cells in culture expressed Faah, coding for the NAE hydrolytic enzyme fatty acid amide hydrolase, at much lower levels than Naaa. However, the ability of the intact cells to hydrolyse the NAE arachidonoylethanolamide (anandamide) was inhibited by an inhibitor of FAAH, but not of NAAA. Treatment of the AT1 cells with interleukin-6, a cytokine known to be involved in the pathogenesis of prostate cancer, did not affect the expression of the components of the NAE/MAG system studied. It is thus concluded that in the model system studied, the tumours show different expressions of mRNA coding for key the components of the NAE/MAG system compared to the host tissue, but that these changes are not accompanied by alterations in the non-malignant tissue.

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  • 13. Allas, Ular
    et al.
    Toom, Lauri
    Selyutina, Anastasia
    Maeorg, Uno
    Medina, Ricardo
    Merits, Andres
    Rinken, Ago
    Hauryliuk, Vasili
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). University of Tartu, Institute of Technology, Nooruse 1, Tartu 50411, Estonia.
    Kaldalu, Niilo
    Tenson, Tanel
    Antibacterial activity of the nitrovinylfuran G1 (Furvina) and its conversion products2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 36844Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    2-Bromo-5-(2-bromo-2-nitrovinyl) furan (G1 or Furvina) is an antimicrobial with a direct reactivity against thiol groups. It is active against Gram-positive and Gram-negative bacteria, yeasts and filamentous fungi. By reacting with thiol groups it causes direct damage to proteins but, as a result, is very short-living and interconverts into an array of reaction products. Our aim was to characterize thiol reactivity of G1 and its conversion products and establish how much of antimicrobial and cytotoxic effects are due to the primary activity of G1 and how much can be attributed to its reaction products. Stability of G1 in growth media as well as its conversion in the presence of thiols was characterized. The structures of G1 decomposition products were determined using NMR and mass-spectroscopy. Concentration-and time-dependent killing curves showed that G1 is bacteriostatic for Escherichia coli at the concentration of 16 mu g/ml and bactericidal at 32 mu g/ml. However, G1 is inefficient against non-growing E. coli. Addition of cysteine to medium reduces the antimicrobial potency of G1. Nevertheless, the reaction products of G1 and cysteine enabled prolonged antimicrobial action of the drug. Therefore, the activity of 2-bromo-5-(2-bromo-2-nitrovinyl) furan is a sum of its immediate reactivity and the antibacterial effects of the conversion products.

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  • 14.
    Alling, Teodor
    et al.
    Department of Forest Biomaterials and Technology, Swedish University of Agricultural Sciences, Umeå, Sweden; Department of Biology, Lund University, Lund, Sweden.
    Funk, Christiane
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Gentili, Francesco G.
    Department of Forest Biomaterials and Technology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Nordic microalgae produce biostimulant for the germination of tomato and barley seeds2023Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 13, nr 1, artikel-id 3509Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Microalgal biomass may have biostimulating effects on plants and seeds due to its phytohormonal content, and harnessing this biostimulating effect could contribute to sustainable agriculture. Two Nordic strains of freshwater microalgae species Chlorella vulgaris and Scenedesmus obliquus were each cultivated in a photobioreactor receiving untreated municipal wastewater. The algal biomass and the supernatant after algal cultivation were tested on tomato and barley seeds for biostimulating effects. Intact algal cells, broken cells, or harvest supernatant were applied to the seeds, and germination time, percentage and germination index were evaluated. Seeds treated with C. vulgaris, in particular intact cells or supernatant, had up to 25 percentage units higher germination percentage after 2 days and an overall significantly faster germination time (germinated on average between 0.5 and 1 day sooner) than seeds treated with S. obliquus or the control (water). The germination index was higher in C. vulgaris treatments than in the control for both tomato and barley, and this was observed for both broken and intact cells as well as supernatant. The Nordic strain of C. vulgaris cultivated in municipal wastewater thus shows potential for use as biostimulant in agriculture, adding novel economic and sustainability benefits.

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  • 15. Almlöf, Jonas Carlsson
    et al.
    Alexsson, Andrei
    Imgenberg-Kreuz, Juliana
    Sylwan, Lina
    Backlin, Christofer
    Leonard, Dag
    Nordmark, Gunnel
    Tandre, Karolina
    Eloranta, Maija-Leena
    Padyukov, Leonid
    Bengtsson, Christine
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Jonsen, Andreas
    Dahlqvist, Solbritt Rantapaa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sjowall, Christopher
    Bengtsson, Anders A.
    Gunnarsson, Iva
    Svenungsson, Elisabet
    Ronnblom, Lars
    Sandling, Johanna K.
    Syvanen, Ann-Christine
    Novel risk genes for systemic lupus erythematosus predicted by random forest classification2017Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 7, artikel-id 6236Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genome-wide association studies have identified risk loci for SLE, but a large proportion of the genetic contribution to SLE still remains unexplained. To detect novel risk genes, and to predict an individual's SLE risk we designed a random forest classifier using SNP genotype data generated on the "Immunochip" from 1,160 patients with SLE and 2,711 controls. Using gene importance scores defined by the random forest classifier, we identified 15 potential novel risk genes for SLE. Of them 12 are associated with other autoimmune diseases than SLE, whereas three genes (ZNF804A, CDK1, and MANF) have not previously been associated with autoimmunity. Random forest classification also allowed prediction of patients at risk for lupus nephritis with an area under the curve of 0.94. By allele-specific gene expression analysis we detected cis-regulatory SNPs that affect the expression levels of six of the top 40 genes designed by the random forest analysis, indicating a regulatory role for the identified risk variants. The 40 top genes from the prediction were overrepresented for differential expression in B and T cells according to RNA-sequencing of samples from five healthy donors, with more frequent over-expression in B cells compared to T cells.

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  • 16.
    Andersson, Agneta
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå marina forskningscentrum (UMF).
    Ahlinder, J.
    Mathisen, Peter
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Hagglund, M.
    Backman, S.
    Nilsson, E.
    Sjodin, A.
    Thelaus, J.
    Predators and nutrient availability favor protozoa-resisting bacteria in aquatic systems2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 8415Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The long co-existence of bacteria and protozoa has led to the development of bacterial protozoa resistance strategies, which are suggested to serve as drivers for the evolution of pathogenic bacteria. However, the ecological mechanisms underpinning selection for protozoa-resistance in aquatic bacteria are poorly known. To assess the role of nutrient availability and predation-pressure on selection for protozoa-resisting bacteria (PRB), an enrichment-dilution experiment was designed using laboratory microcosms containing natural lake water. PRB was monitored by screening 16S rRNA amplicon sequence data for reads assigned to bacteria that previously has been shown to resist degradation by amoebae. To estimate the effects of the microbial food web dynamics (microscopy of; heterotrophic bacteria, phytoplankton, protozoa and rotifers) and physicochemical variables on the PRB abundance in the study system, a joint species distribution modelling approach was used. The predation-pressure (ratio between predator and bacterial biomass) had a positive effect on the abundance of the PRB genus Mycobacterium, while perturbation (enrichment and dilution) favored the PRB genus Pseudomonas that dominated the bacterial community in the disturbed systems. Our results show that PRB with different ecological strategies can be expected in water of high and intermediate nutrient levels and after major disturbances of an aquatic system.

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  • 17.
    Andersson, Gustav
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Handkirurgi.
    Orädd, Greger
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB). Umeå universitet, Medicinska fakulteten, Umeå Centre for Comparative Biology (UCCB).
    Sultan, Fahad
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Novikov, Lev N.
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    In vivo Diffusion Tensor Imaging, Diffusion Kurtosis Imaging, and Tractography of a Sciatic Nerve Injury Model in Rat at 9.4T2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 12911Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Peripheral nerve injuries result in severe loss of sensory and motor functions in the afflicted limb. There is a lack of standardised models to non-invasively study degeneration, regeneration, and normalisation of neuronal microstructure in peripheral nerves. This study aimed to develop a non-invasive evaluation of peripheral nerve injuries, using diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and tractography on a rat model of sciatic nerve injury. 10 female Sprague Dawley rats were exposed to sciatic nerve neurotmesis and studied using a 9.4 T magnet, by performing DTI and DKI of the sciatic nerve before and 4 weeks after injury. The distal nerve stump showed a decrease in fractional anisotropy (FA), mean kurtosis (MK), axonal water fraction (AWF), and radial and axonal kurtosis (RK, AK) after injury. The proximal stump showed a significant decrease in axial diffusivity (AD) and increase of MK and AK as compared with the uninjured nerve. Both mean diffusivity (MD) and radial diffusivity (RD) increased in the distal stump after injury. Tractography visualised the sciatic nerve and the site of injury, as well as local variations of the diffusion parameters following injury. In summary, the described method detects changes both proximal and distal to the nerve injury.

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  • 18.
    Andresen, Liis
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Tenson, Tanel
    Hauryliuk, Vasili
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Cationic bactericidal peptide 1018 does not specifically target the stringent response alarmone (p)ppGpp2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 36549Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The bacterial stringent response is a key regulator of bacterial virulence, biofilm formation and antibiotic tolerance, and is a promising target for the development of new antibacterial compounds. The intracellular nucleotide (p)ppGpp acts as a messenger orchestrating the stringent response. A synthetic peptide 1018 was recently proposed to specifically disrupt biofilms by inhibiting the stringent response via direct interaction with (p) ppGpp (de la Fuente-Nunez et al. (2014) PLoS Pathogens). We have interrogated the specificity of the proposed molecular mechanism. When inhibition of Pseudomonas aeruginosa planktonic and biofilm growth is tested simultaneously in the same assay, peptides 1018 and the control peptide 8101 generated by an inversion of the amino acid sequence of 1018 are equally potent, and, importantly, do not display a preferential activity against biofilm. 1018 inhibits planktonic growth of Escherichia coli equally efficiently either when the alleged target, (p) ppGpp, is essential (MOPS media lacking amino acid L-valine), or dispensable for growth (MOPS media supplemented with L-valine). Genetic disruption of the genes relA and spoT responsible for (p) ppGpp synthesis moderately sensitizes-rather than protects-E. coli to 1018. We suggest that the antimicrobial activity of 1018 does not rely on specific recognition of the stringent response messenger (p) ppGpp.

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  • 19.
    Andresen, Liis
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Varik, Vallo
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Tozawa, Yuzuru
    Jimmy, Steffi
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Lindberg, Stina
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Tenson, Tanel
    Hauryliuk, Vasili
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). University of Tartu, Institute of Technology, Nooruse 1, 50411 Tartu, Estonia.
    Auxotrophy-based High Throughput Screening assay for the identification of Bacillus subtilis stringent response inhibitors2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 35824Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The stringent response is a central adaptation mechanism that allows bacteria to adjust their growth and metabolism according to environmental conditions. The functionality of the stringent response is crucial for bacterial virulence, survival during host invasion as well as antibiotic resistance and tolerance. Therefore, specific inhibitors of the stringent response hold great promise as molecular tools for disarming and pacifying bacterial pathogens. By taking advantage of the valine amino acid auxotrophy of the Bacillus subtilis stringent response-deficient strain, we have set up a High Throughput Screening assay for the identification of stringent response inhibitors. By screening 17,500 compounds, we have identified a novel class of antibacterials based on the 4-(6-(phenoxy) alkyl)-3,5-dimethyl-1H-pyrazole core. Detailed characterization of the hit compounds as well as two previously identified promising stringent response inhibitors-a ppGpp-mimic nucleotide Relacin and cationic peptide 1018 - showed that neither of the compounds is sufficiently specific, thus motivating future application of our screening assay to larger and more diverse molecular libraries.

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  • 20.
    Annamalai, Alagappan
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Division of Biotechnology, Advanced Institute of Environmental and Bioscience, College of Environmental and Bioresource Sciences, Chonbuk National University, Republic of Korea.
    Lee, Hyun Hwi
    Choi, Sun Hee
    Lee, Su Yong
    Gracia-Espino, Eduardo
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Subramanian, Arunprabaharan
    Park, Jaedeuk
    Kong, Ki-jeong
    Jang, Jum Suk
    Sn/Be Sequentially co-doped Hematite Photoanodes for Enhanced Photoelectrochemical Water Oxidation: Effect of Be2+ as co-dopant2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 23183Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    For ex-situ co-doping methods, sintering at high temperatures enables rapid diffusion of Sn4+ and Be2+ dopants into hematite (alpha-Fe2O3) lattices, without altering the nanorod morphology or damaging their crystallinity. Sn/Be co-doping results in a remarkable enhancement in photocurrent (1.7 mA/cm(2)) compared to pristine alpha-Fe2O3 (0.7 mA/cm(2)), and Sn4+ mono-doped alpha-Fe2O3 photoanodes (1.0 mA/cm(2)). From first-principles calculations, we found that Sn4+ doping induced a shallow donor level below the conduction band minimum, which does not contribute to increase electrical conductivity and photocurrent because of its localized nature. Additionally, Sn4+-doping induce local micro-strain and a decreased Fe-O bond ordering. When Be2+ was co-doped with Sn4+-doped alpha-Fe2O3 photoanodes, the conduction band recovered its original state, without localized impurities peaks, also a reduction in micro-strain and increased Fe-O bond ordering is observed. Also the sequence in which the ex-situ co-doping is carried out is very crucial, as Be/Sn co-doping sequence induces many under-coordinated O atoms resulting in a higher micro-strain and lower charge separation efficiency resulting undesired electron recombination. Here, we perform a detailed systematic characterization using XRD, FESEM, XPS and comprehensive electrochemical and photoelectrochemical studies, along with sophisticated synchrotron diffraction studies and extended X-ray absorption fine structure.

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  • 21. Ardini, Matteo
    et al.
    Huang, Jian-An
    Sánchez, Carlos S.
    Mousavi, Mansoureh Z.
    Caprettini, Valeria
    Maccaferri, Nicolò
    Istituto Italiano di Tecnologia, Genova, Italy.
    Melle, Giovanni
    Bruno, Giulia
    Pasquale, Lea
    Garoli, Denis
    De Angelis, Francesco
    Live Intracellular Biorthogonal Imaging by Surface Enhanced Raman Spectroscopy using Alkyne-Silver Nanoparticles Clusters2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, nr 1, artikel-id 12652Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Live intracellular imaging is a valuable tool in modern diagnostics and pharmacology. Surface Enhanced Raman Spectroscopy (SERS) stands out as a non-destructive and multiplexed technique, but intracellular SERS imaging still suffers from interfering background from endogenous components. Here we show the assembly of small colloidal SERS probes with Raman signal in the cell-silent window of 1800–2900 cm−1 for biorthogonal intracellular SERS imaging of dopamine that was undistinguishable from the endogenous cell background. By linking colloidal silver nanoparticles with alkyne-dopamine adducts, clusters are formed by 2–6 nanoparticles spaced by tight interparticle gaps that exhibited high electric field enhancement and strong SERS signals of alkyne and dopamines. Due to the cell-silent signals of the alkyne, intracellular in-vitro Raman imaging shows that the dopamines on the internalized clusters remain distinguishable across the cytoplasm with good spatial resolution. Our method can be a general-purpose method for real-time imaging of biomolecules, such as proteins, peptides, DNA and drugs.

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  • 22.
    Arumugam, Ashokan
    et al.
    Department of Physiotherapy, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
    Häger, Charlotte
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi.
    Thigh muscle co-contraction patterns in individuals with anterior cruciate ligament reconstruction, athletes and controls during a novel double-hop test2022Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, artikel-id 8431Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Efficient neuromuscular coordination of the thigh muscles is crucial in maintaining dynamic knee stability and thus reducing anterior cruciate ligament (ACL) injury/re-injury risk. This cross-sectional study measured electromyographic (EMG) thigh muscle co-contraction patterns during a novel one-leg double-hop test among individuals with ACL reconstruction (ACLR; n = 34), elite athletes (n = 22) and controls (n = 24). Participants performed a forward hop followed by a 45° unanticipated diagonal hop either in a medial (UMDH) or lateral direction (ULDH). Medial and lateral quadriceps and hamstrings EMG were recorded for one leg (injured/non-dominant). Quadriceps-to-Hamstring (Q:H) ratio, lateral and medial Q:H co-contraction indices (CCIs), and medial-to-lateral Q:H co-contraction ratio (CCR; a ratio of CCIs) were calculated for three phases (100 ms prior to landing, initial contact [IC] and deceleration phases) of landing. We found greater activity of the quadriceps than the hamstrings during the IC and deceleration phases of UMDH/ULDH across groups. However, higher co-contraction of medial rather than lateral thigh muscles during the deceleration phase of landing was found; if such co-contraction patterns cause knee adduction, a putative mechanism to decrease ACL injury risk, during the deceleration phase of landing across groups warrants further investigation.

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  • 23. Asghar, Naveed
    et al.
    Lee, Yi-Ping
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Nilsson, Emma
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Lindqvist, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Melik, Wessam
    Kröger, Andrea
    Överby, Anna K.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Johansson, Magnus
    The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 39265Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The tick-borne encephalitis virus (TBEV) is a flavivirus transmitted to humans, usually via tick bites. The virus causes tick-borne encephalitis (TBE) in humans, and symptoms range from mild flu-like symptoms to severe and long-lasting sequelae, including permanent brain damage. It has been suggested that within the population of viruses transmitted to the mammalian host, quasispecies with neurotropic properties might become dominant in the host resulting in neurological symptoms. We previously demonstrated the existence of TBEV variants with variable poly(A) tracts within a single blood-fed tick. To characterize the role of the poly(A) tract in TBEV replication and virulence, we generated infectious clones of Toro-2003 with the wild-type (A)(3)C(A)(6) sequence (Toro-6A) or with a modified (A)(3)C(A)(38) sequence (Toro-38A). Toro-38A replicated poorly compared to Toro-6A in cell culture, but Toro-38A was more virulent than Toro-6A in a mouse model of TBE. Next-generation sequencing of TBEV genomes after passaging in cell culture and/or mouse brain revealed mutations in specific genomic regions and the presence of quasispecies that might contribute to the observed differences in virulence. These data suggest a role for quasispecies development within the poly(A) tract as a virulence determinant for TBEV in mice.

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  • 24. Atabaki-Pasdar, Naeimeh
    et al.
    Ohlsson, Mattias
    Shungin, Dmitry
    Kurbasic, Azra
    Ingelsson, Erik
    Pearson, Ewan R.
    Ali, Ashfaq
    Franks, Paul W.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, SE-205 02, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Statistical power considerations in genotype-based recall randomized controlled trials2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 37307Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for genemetformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a metformin transported encoding locus. We then calculated statistical power for interactions between genetic risk scores (GRS), metformin treatment and intensive lifestyle intervention (ILI) given a range of sampling frames, clinical trial sample sizes, interaction effect estimates, and allele frequencies; outcomes were type 2 diabetes incidence (time-to-event) and change in small LDL particles (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR (participants recruited from the extremes of a GRS distribution) and conventional sampling (participants recruited without explicit emphasis on genetic characteristics). We further examined the influence of outcome measurement error on statistical power. Under most simulated scenarios, GBR trials have substantially higher power to observe gene-drug and gene-lifestyle interactions than same-sized conventional RCTs. GBR trials are becoming popular for validation of gene-treatment interactions; our analyses illustrate the strengths and weaknesses of this design.

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  • 25.
    Bano, Fouzia
    et al.
    CIC biomaGUNE, Donostia-San Sebastian, Spain.
    Banerji, Suneale
    Howarth, Mark
    Jackson, David G.
    Richter, Ralf P.
    A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 34176Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glycosaminoglycans (GAGs), a category of linear, anionic polysaccharides, are ubiquitous in the extracellular space, and important extrinsic regulators of cell function. Despite the recognized significance of mechanical stimuli in cellular communication, however, only few single molecule methods are currently available to study how monovalent and multivalent GAG·protein bonds respond to directed mechanical forces. Here, we have devised such a method, by combining purpose-designed surfaces that afford immobilization of GAGs and receptors at controlled nanoscale organizations with single molecule force spectroscopy (SMFS). We apply the method to study the interaction of the GAG polymer hyaluronan (HA) with CD44, its receptor in vascular endothelium. Individual bonds between HA and CD44 are remarkably resistant to rupture under force in comparison to their low binding affinity. Multiple bonds along a single HA chain rupture sequentially and independently under load. We also demonstrate how strong non-covalent bonds, which are versatile for controlled protein and GAG immobilization, can be effectively used as molecular anchors in SMFS. We thus establish a versatile method for analyzing the nanomechanics of GAG·protein interactions at the level of single GAG chains, which provides new molecular-level insight into the role of mechanical forces in the assembly and function of GAG-rich extracellular matrices.

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  • 26.
    Barceló, Isabel M.
    et al.
    Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
    Escobar-Salom, María
    Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
    Jordana-Lluch, Elena
    Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
    Torrens, Gabriel
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Oliver, Antonio
    Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
    Juan, Carlos
    Health Research Institute of the Balearic Islands (IdISBa), Palma, Spain; Microbiology Department, University Hospital Son Espases (HUSE), Palma, Spain; Centro de Investigación Biomédica en Red, Área Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.
    Filling knowledge gaps related to AmpC-dependent β-lactam resistance in Enterobacter cloacae2024Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 14, nr 1, artikel-id 189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Enterobacter cloacae starred different pioneer studies that enabled the development of a widely accepted model for the peptidoglycan metabolism-linked regulation of intrinsic class C cephalosporinases, highly conserved in different Gram-negatives. However, some mechanistic and fitness/virulence-related aspects of E. cloacae choromosomal AmpC-dependent resistance are not completely understood. The present study including knockout mutants, β-lactamase cloning, gene expression analysis, characterization of resistance phenotypes, and the Galleria mellonella infection model fills these gaps demonstrating that: (i) AmpC enzyme does not show any collateral activity impacting fitness/virulence; (ii) AmpC hyperproduction mediated by ampD inactivation does not entail any biological cost; (iii) alteration of peptidoglycan recycling alone or combined with AmpC hyperproduction causes no attenuation of E. cloacae virulence in contrast to other species; (iv) derepression of E. cloacae AmpC does not follow a stepwise dynamics linked to the sequential inactivation of AmpD amidase homologues as happens in Pseudomonas aeruginosa; (v) the enigmatic additional putative AmpC-type β-lactamase generally present in E. cloacae does not contribute to the classical cephalosporinase hyperproduction-based resistance, having a negligible impact on phenotypes even when hyperproduced from multicopy vector. This study reveals interesting particularities in the chromosomal AmpC-related behavior of E. cloacae that complete the knowledge on this top resistance mechanism.

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  • 27. Baumann, Anne
    et al.
    Jorge-Finnigan, Ana
    Jung-KC, Kunwar
    Sauter, Alexander
    Horvath, Istvan
    Morozova-Roche, Ludmilla A.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Martinez, Aurora
    Tyrosine Hydroxylase Binding to Phospholipid Membranes Prompts Its Amyloid Aggregation and Compromises Bilayer Integrity2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 39488Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tyrosine hydroxylase (TH), a rate-limiting enzyme in the synthesis of catecholamine neurotransmitters and hormones, binds to negatively charged phospholipid membranes. Binding to both large and giant unilamellar vesicles causes membrane permeabilization, as observed by efflux and influx of fluorescence dyes. Whereas the initial protein-membrane interaction involves the N-terminal tail that constitutes an extension of the regulatory ACT-domain, prolonged membrane binding induces misfolding and self-oligomerization of TH over time as shown by circular dichroism and Thioflavin T fluorescence. The gradual amyloid-like aggregation likely occurs through cross-beta interactions involving aggregation-prone motives in the catalytic domains, consistent with the formation of chain and ring-like protofilaments observed by atomic force microscopy in monolayer-bound TH. PC12 cells treated with the neurotoxin 6-hydroxydopamine displayed increased TH levels in the mitochondrial fraction, while incubation of isolated mitochondria with TH led to a decrease in the mitochondrial membrane potential. Furthermore, cell-substrate impedance and viability assays showed that supplementing the culture media with TH compromises cell viability over time. Our results revealed that the disruptive effect of TH on cell membranes may be a cytotoxic and pathogenic factor if the regulation and intracellular stability of TH is compromised.

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  • 28. Beer, Christian
    et al.
    Zimov, Nikita
    Olofsson, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap.
    Porada, Philipp
    Zimov, Sergey
    Protection of Permafrost Soils from Thawing by Increasing Herbivore Density2020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 4170Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Climate change will cause a substantial future greenhouse gas release from warming and thawing permafrost-affected soils to the atmosphere enabling a positive feedback mechanism. Increasing the population density of big herbivores in northern high-latitude ecosystems will increase snow density and hence decrease the insulation strength of snow during winter. As a consequence, theoretically 80% of current permafrost-affected soils (<10 m) is projected to remain until 2100 even when assuming a strong warming using the Representative Concentration Pathway 8.5. Importantly, permafrost temperature is estimated to remain below -4<degrees>C on average after increasing herbivore population density. Such ecosystem management practices would be therefore theoretically an important additional climate change mitigation strategy. Our results also highlight the importance of new field experiments and observations, and the integration of fauna dynamics into complex Earth System models, in order to reliably project future ecosystem functions and climate.

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  • 29.
    Behzadi, Arvin
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Pujol-Calderón, Fani
    Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden.
    Tjust, Anton E.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Wuolikainen, Anna
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Höglund, Kina
    Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Forsberg, Karin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Portelius, Erik
    Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Blennow, Kaj
    Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.
    Zetterberg, Henrik
    Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom; UK Dementia Research Institute at UCL, London, United Kingdom.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Neurofilaments can differentiate ALS subgroups and ALS from common diagnostic mimics2021Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 22128Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Delayed diagnosis and misdiagnosis are frequent in people with amyotrophic lateral sclerosis (ALS), the most common form of motor neuron disease (MND). Neurofilament light chain (NFL) and phosphorylated neurofilament heavy chain (pNFH) are elevated in ALS patients. We retrospectively quantified cerebrospinal fluid (CSF) NFL, CSF pNFH and plasma NFL in stored samples that were collected at the diagnostic work-up of ALS patients (n = 234), ALS mimics (n = 44) and controls (n = 9). We assessed the diagnostic performance, prognostication value and relationship to the site of onset and genotype. CSF NFL, CSF pNFH and plasma NFL levels were significantly increased in ALS patients compared to patients with neuropathies & myelopathies, patients with myopathies and controls. Furthermore, CSF pNFH and plasma NFL levels were significantly higher in ALS patients than in patients with other MNDs. Bulbar onset ALS patients had significantly higher plasma NFL levels than spinal onset ALS patients. ALS patients with C9orf72HRE mutations had significantly higher plasma NFL levels than patients with SOD1 mutations. Survival was negatively correlated with all three biomarkers. Receiver operating characteristics showed the highest area under the curve for CSF pNFH for differentiating ALS from ALS mimics and for plasma NFL for estimating ALS short and long survival. All three biomarkers have diagnostic value in differentiating ALS from clinically relevant ALS mimics. Plasma NFL levels can be used to differentiate between clinical and genetic ALS subgroups.

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  • 30. Beljantseva, Jelena
    et al.
    Kudrin, Pavel
    Jimmy, Steffi
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Ehn, Marcel
    Pohl, Radek
    Varik, Vallo
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). 1University of Tartu, Institute of Technology, Tartu, Estonia.
    Tozawa, Yuzuru
    Shingler, Victoria
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet).
    Tenson, Tanel
    Rejman, Dominik
    Hauryliuk, Vasili
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). 1University of Tartu, Institute of Technology, Tartu, Estonia.
    Molecular mutagenesis of ppGpp: turning a RelA activator into an inhibitor2017Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 7, artikel-id 41839Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The alarmone nucleotide (p) ppGpp is a key regulator of bacterial metabolism, growth, stress tolerance and virulence, making (p) ppGpp-mediated signaling a promising target for development of antibacterials. Although ppGpp itself is an activator of the ribosome-associated ppGpp synthetase RelA, several ppGpp mimics have been developed as RelA inhibitors. However promising, the currently available ppGpp mimics are relatively inefficient, with IC50 in the sub-mM range. In an attempt to identify a potent and specific inhibitor of RelA capable of abrogating (p) ppGpp production in live bacterial cells, we have tested a targeted nucleotide library using a biochemical test system comprised of purified Escherichia coli components. While none of the compounds fulfilled this aim, the screen has yielded several potentially useful molecular tools for biochemical and structural work.

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  • 31.
    Bellieny-Rabelo, Daniel
    et al.
    Laboratório de Química e Função de Proteínas e Peptídeos, Centro de Biociências e Biotecnologia, Universidade Estadual do Norte Fluminense Darcy Ribeiro, Campos dos Goytacazes, Brazil.
    De Oliveira, Eduardo Alves Gamosa
    Ribeiro, Elane da Silva
    Costa, Evenilton Pessoa
    Oliveira, Antônia Elenir Amâncio
    Venancio, Thiago Motta
    Transcriptome analysis uncovers key regulatory and metabolic aspects of soybean embryonic axes during germination2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 36009Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Soybean (Glycine max) is a major legume crop worldwide, providing a critical source of protein and oil. The release of the soybean genome fuelled several transcriptome projects comprising multiple developmental stages and environmental conditions. Nevertheless, the global transcriptional patterns of embryonic axes during germination remain unknown. Here we report the analysis of ~1.58 billion RNA-Seq reads from soybean embryonic axes at five germination stages. Our results support the early activation of processes that are critical for germination, such as glycolysis, Krebs cycle and cell wall remodelling. Strikingly, only 3 hours after imbibition there is a preferential up-regulation of protein kinases and transcription factors, particularly from the LOB domain family, implying that transcriptional and post-transcriptional regulation play major roles early after imbibition. Lipid mobilization and glyoxylate pathways are also transcriptionally active in the embryonic axes, indicating that the local catabolism of oil reserves in the embryonic axes contributes to energy production during germination. We also present evidence supporting abscisic acid inactivation and the up-regulation of gibberellin, ethylene and brassinosteroid pathways. Further, there is a remarkable differential activation of paralogous genes in these hormone signalling pathways. Taken together, our results provide insights on the regulation and biochemistry of soybean germination.

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  • 32. Berdahl, Andrew
    et al.
    Brelsford, Christa
    De Bacco, Caterina
    Dumas, Marion
    Ferdinand, Vanessa
    Grochow, Joshua A.
    Hebert-Dufresne, Laurent
    Kallus, Yoav
    Kempes, Christopher P.
    Kolchinsky, Artemy
    Larremore, Daniel B.
    Libby, Eric
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för matematik och matematisk statistik.
    Power, Eleanor A.
    Stern, Caitlin A.
    Tracey, Brendan D.
    Dynamics of beneficial epidemics2019Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 9, artikel-id 15093Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Pathogens can spread epidemically through populations. Beneficial contagions, such as viruses that enhance host survival or technological innovations that improve quality of life, also have the potential to spread epidemically. How do the dynamics of beneficial biological and social epidemics differ from those of detrimental epidemics? We investigate this question using a breadth-first modeling approach involving three distinct theoretical models. First, in the context of population genetics, we show that a horizontally-transmissible element that increases fitness, such as viral DNA, spreads superexponentially through a population, more quickly than a beneficial mutation. Second, in the context of behavioral epidemiology, we show that infections that cause increased connectivity lead to superexponential fixation in the population. Third, in the context of dynamic social networks, we find that preferences for increased global infection accelerate spread and produce superexponential fixation, but preferences for local assortativity halt epidemics by disconnecting the infected from the susceptible. We conclude that the dynamics of beneficial biological and social epidemics are characterized by the rapid spread of beneficial elements, which is facilitated in biological systems by horizontal transmission and in social systems by active spreading behavior of infected individuals.

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  • 33.
    Berdynski, Mariusz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper. Laboratory of Neurogenetics, Department of Neurodegenerative Disorders, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
    Miszta, Przemysław
    Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland.
    Safranow, Krzysztof
    Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 72 Powstańców Wlkp. Str., Szczecin, Poland.
    Andersen, Peter M.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Morita, Mitsuya
    Division of Neurology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Japan.
    Filipek, Sławomir
    Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Warsaw, Poland.
    Żekanowski, Cezary
    Laboratory of Neurogenetics, Department of Neurodegenerative Disorders, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
    Kuźma-Kozakiewicz, Magdalena
    Department of Neurology, Medical University of Warsaw, Warsaw, Poland; Neurodegenerative Diseases Research Group, Medical University of Warsaw, Warsaw, Poland.
    SOD1 mutations associated with amyotrophic lateral sclerosis analysis of variant severity2022Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, nr 1, artikel-id 103Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mutations in superoxide dismutase 1 gene (SOD1) are linked to amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder predominantly affecting upper and lower motor neurons. The clinical phenotype of ALS shows inter- and intrafamilial heterogeneity. The aim of the study was to analyze the relations between individual SOD1 mutations and the clinical presentation using in silico methods to assess the SOD1 mutations severity. We identified SOD1 causative variants in a group of 915 prospectively tested consecutive Polish ALS patients from a neuromuscular clinical center, performed molecular modeling of mutated SOD1 proteins and in silico analysis of mutation impact on clinical phenotype and survival analysis of associations between mutations and hazard of clinical end-points. Fifteen SOD1 mutations were identified in 21.1% familial and 2.3% sporadic ALS cases. Their effects on SOD1 protein structure and functioning inferred from molecular modeling and in silico analyses correlate well with the clinical data. Molecular modeling results support the hypothesis that folding intermediates rather than mature SOD1 protein give rise to the source of cytotoxic conformations in ALS. Significant associations between type of mutation and clinical end-points were found.

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  • 34. Berger, Eloise
    et al.
    Delpierre, Cyrille
    Hosnijeh, Fatemeh Saberi
    Kelly-Irving, Michelle
    Portengen, Lutzen
    Bergdahl, Ingvar
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning.
    Johansson, Ann Sofie
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Krogh, Vittorio
    Palli, Domenico
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Kyrtopoulos, Soterios A.
    Vineis, Paolo
    Chadeau-Hyam, Marc
    Vermeulen, Roel
    Castagné, Raphaële
    Association between low-grade inflammation and Breast cancer and B-cell Myeloma and Non-Hodgkin Lymphoma: findings from two prospective cohorts2018Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 8, artikel-id 10805Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Chronic inflammation may be involved in cancer development and progression. Using 28 inflammatory-related proteins collected from prospective blood samples from two case-control studies nested in the Italian component of the European Prospective Investigation into Cancer and nutrition (n = 261) and in the Northern Sweden Health and Disease Study (n = 402), we tested the hypothesis that an inflammatory score is associated with breast cancer (BC) and.-cell Non-Hodgkin Lymphoma (B-cell NHL, including 68 multiple myeloma cases) onset. We modelled the relationship between this inflammatory score and the two cancers studied: (BC and B-cell NHL) using generalised linear models, and assessed, through adjustments the role of behaviours and lifestyle factors. Analyses were performed by cancer types pooling both populations, and stratified by cohorts, and time to diagnosis. Our results suggested a lower inflammatory score in B-cell NHL cases (β = -1.28, p = 0.012), and, to lesser, extent with BC (β= -0.96, p = 0.33) compared to controls, mainly driven by cancer cases diagnosed less than 6 years after enrolment. These associations were not affected by subsequent adjustments for potential intermediate confounders, notably behaviours. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated. These observations call for further studies involving larger populations, larger variety of cancer types and repeated measures of larger panel of inflammatory markers.

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  • 35. Bergquist, Maria
    et al.
    Samuelsson, Line
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Larsson, Anders
    Tydén, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Johansson, Joakim
    Lipcsey, Miklos
    TNFR1, TNFR2, neutrophil gelatinase-associated lipocalin and heparin binding protein in identifying sepsis and predicting outcome in an intensive care cohort2020Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 10, nr 1, artikel-id 15350Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To date no biomarkers can aid diagnosing sepsis with adequate accuracy. We set out to assess the ability of Tumor necrosis factor receptor (TNFR) 1 and 2, Neutrophil gelatinase-associated lipocalin (NGAL) and Heparin binding protein (HBP) to discriminate sepsis from non-infected critically ill patients in a large ICU cohort, and to evaluate their value to predict mortality at 30 days. Adult patients admitted to the ICU with an arterial catheter were included. Clinical data and blood samples were prospectively recorded daily. Diagnoses were set retrospectively. Descriptive statistics and logistic regression models were used. NGAL, TNFR1 and TNFR2 were higher in sepsis patients compared to other diagnoses, as well as in non-survivors compared to survivors. In addition, these biomarkers increased with increasing stages of acute kidney injury. TNFR1 and TNFR2 performed similarly to NGAL and CRP in identifying sepsis patients, but they performed better than CRP in predicting 30-day mortality in this ICU cohort. Thus, TNFR1 and TNFR2 may be particularly useful in identifying high risk sepsis patients and facilitate relevant health care actions in this group of sepsis patients.

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  • 36.
    Bergström, Kristofer
    et al.
    Department of Biology and Environmental Science, Centre for Ecology and Evolution in Microbial Model Systems EEMiS, Linnaeus University, Kalmar, Sweden.
    Nordahl, Oscar
    Söderling, Peter
    Koch-Schmidt, Per
    Borger, Tobias
    Tibblin, Petter
    Larsson, Per
    Exceptional longevity in northern peripheral populations of Wels catfish (Silurus glanis)2022Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, nr 1, artikel-id 8070Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Studies of life-history variation across a species range are crucial for ecological understanding and successful conservation. Here, we examined the growth and age of Wels catfish (Silurus glanis) in Sweden, which represent the northernmost populations in Europe. A total of 1183 individuals were captured, marked and released between 2006 and 2020. Mark-recapture data from 162 individuals (size range: 13–195 cm) were used to estimate von Bertalanffy growth curve parameters which revealed very slow growth rates compared to catfish within the core distribution area (central Europe). The fitted von Bertalanffy growth curve predicted a 150 cm catfish to be around 40 years old, while the largest recaptured individual (length 195 cm) was estimated to be 70 (95% CI 50–112) years old. This was substantially older than the previously documented maximum age of a catfish. The weight at length relationships in these northern peripheral populations were similar to those documented for catfish in central Europe indicating that resources did not constrain growth. This indicates that the slow growth and exceptional high age in the northern catfish populations are the result of lower temperatures and/or local adaptations.

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    errata
  • 37.
    Berntsson, Elina
    et al.
    Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden; Department of Chemistry and Biotechnology, Tallinn University of Technology, Tallinn, Estonia.
    Vosough, Faraz
    Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden.
    Svantesson, Teodor
    Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden.
    Pansieri, Jonathan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Iashchishyn, Igor
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ostojic, Lucija
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Dong, Xiaolin
    Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden.
    Paul, Suman
    Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden.
    Jarvet, Jüri
    Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden; National Institute of Chemical Physics and Biophysics, Tallinn, Estonia.
    Roos, Per M.
    Institute of Environmental Medicine, Karolinska Institutet, Nobels Väg 13, Stockholm, Sweden; Department of Clinical Physiology, Capio St. Göran Hospital, St. Göransplan 1, Stockholm, Sweden.
    Barth, Andreas
    Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden.
    Morozova-Roche, Ludmilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Gräslund, Astrid
    Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden.
    Wärmländer, Sebastian K T S
    Chemistry Section, Arrhenius Laboratories, Stockholm University, Stockholm, Sweden.
    Residue-specific binding of Ni(II) ions influences the structure and aggregation of amyloid beta (Aβ) peptides2023Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 13, nr 1, artikel-id 3341Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Alzheimer's disease (AD) is the most common cause of dementia worldwide. AD brains display deposits of insoluble amyloid plaques consisting mainly of aggregated amyloid-β (Aβ) peptides, and Aβ oligomers are likely a toxic species in AD pathology. AD patients display altered metal homeostasis, and AD plaques show elevated concentrations of metals such as Cu, Fe, and Zn. Yet, the metal chemistry in AD pathology remains unclear. Ni(II) ions are known to interact with Aβ peptides, but the nature and effects of such interactions are unknown. Here, we use numerous biophysical methods-mainly spectroscopy and imaging techniques-to characterize Aβ/Ni(II) interactions in vitro, for different Aβ variants: Aβ(1-40), Aβ(1-40)(H6A, H13A, H14A), Aβ(4-40), and Aβ(1-42). We show for the first time that Ni(II) ions display specific binding to the N-terminal segment of full-length Aβ monomers. Equimolar amounts of Ni(II) ions retard Aβ aggregation and direct it towards non-structured aggregates. The His6, His13, and His14 residues are implicated as binding ligands, and the Ni(II)·Aβ binding affinity is in the low µM range. The redox-active Ni(II) ions induce formation of dityrosine cross-links via redox chemistry, thereby creating covalent Aβ dimers. In aqueous buffer Ni(II) ions promote formation of beta sheet structure in Aβ monomers, while in a membrane-mimicking environment (SDS micelles) coil-coil helix interactions appear to be induced. For SDS-stabilized Aβ oligomers, Ni(II) ions direct the oligomers towards larger sizes and more diverse (heterogeneous) populations. All of these structural rearrangements may be relevant for the Aβ aggregation processes that are involved in AD brain pathology.

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  • 38.
    Beser, Jessica
    et al.
    Public Health Agency of Sweden, Solna, Sweden; European Centre for Disease Prevention and Control (ECDC), European Public Health Microbiology Training Programme (EUPHEM), Solna, Sweden.
    Galanis, Ilias
    Public Health Agency of Sweden, Solna, Sweden.
    Enkirch, Theresa
    Public Health Agency of Sweden, Solna, Sweden.
    Kühlmann Berenzon, Sharon
    Public Health Agency of Sweden, Solna, Sweden.
    van Straten, Edward
    Public Health Agency of Sweden, Solna, Sweden.
    Duracz, Jan
    Public Health Agency of Sweden, Solna, Sweden.
    Rapp, Marie
    Public Health Agency of Sweden, Solna, Sweden.
    Zakikhany, Katherina
    Public Health Agency of Sweden, Solna, Sweden.
    Mansjö, Mikael
    Public Health Agency of Sweden, Solna, Sweden.
    Wigren, Julia
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Forsell, Mattias N. E.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Groenheit, Ramona
    Public Health Agency of Sweden, Solna, Sweden.
    Tegmark Wisell, Karin
    Public Health Agency of Sweden, Solna, Sweden.
    Bråve, Andreas
    Public Health Agency of Sweden, Solna, Sweden.
    Seroprevalence of SARS-CoV-2 in Sweden, April 26 to May 9, 20212022Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, nr 1, artikel-id 10816Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A national point seroprevalence study of SARS-CoV-2 was conducted in Sweden in April–May 2021. In total, 2860 individuals 3 to 90 years old from a probability-based web panel were included. Results showed that an estimated 32.6% of the population in Sweden had detectable levels of antibodies, and among non-vaccinated 20.1% had detectable levels of antibodies. We tested for differences in seroprevalence between age groups and by sex and estimated seroprevalence among previously infected participants by time since reporting.

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  • 39.
    Besya, Azim-Berdy
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik.
    Grönlund, Andreas
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Intrinsic phenotypic stability of a bi-stable auto regulatory gene2016Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 6, artikel-id 22951Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Even under homogenous conditions clonal cells can assume different distinct states for generations to follow, also known as epigenetic inheritance. Such long periods of different phenotypic states can be formed due to the existence of more than one stable state in the molecule concentration, where the different states are explored through molecular fluctuations. By formulating a single reaction variable representing the birth and death of molecules, including transcription, translation and decay, we calculate the escape time from the phenotypic states attained from autocatalytic synthesis through a Fokker-Planck formulation and integration of an effective pseudo-potential. We calculate the stability of the phenotypic states both for cooperative binding feedback and dimer binding feedback, resulting in non-linear decay.

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  • 40.
    Bitar, Aziz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Aung, Kyaw Min
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Wai, Sun Nyunt
    Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Hammarström, Marie-Louise
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Vibrio cholerae derived outer membrane vesicles modulate the inflammatory response of human intestinal epithelial cells by inducing microRNA-146a2019Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 9, artikel-id 7212Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The small intestinal epithelium of Vibrio cholerae infected patients expresses the immunomodulatory microRNAs miR-146a and miR-155 at acute stage of disease. V. cholerae release outer membrane vesicles (OMVs) that serve as vehicles for translocation of virulence factors including V. cholerae cytolysin (VCC). The aim was to investigate whether OMVs, with and/or without VCC-cargo could be responsible for induction of microRNAs in intestinal epithelial cells and thereby contribute to immunomodulation. Polarized tight monolayers of T84 cells were challenged with OMVs of wildtype and a VCC deletion mutant of the non-O1/non-O139 (NOVC) V. cholerae strain V:5/04 and with soluble VCC. OMVs, with and without VCC-cargo, caused significantly increased levels of miR-146a. Increase was seen already after 2 hours challenge with OMVs and persisted after 12 hours. Challenge with soluble VCC caused significant increases in interleukin-8 (IL-8), tumour necrosis factor-α (TNF-α), CCL20, IL-1β, and IRAK2 mRNA levels while challenge with OMVs did not cause increases in expression levels of any of these mRNAs. These results suggest that V. cholerae bacteria release OMVs that induce miR-146a in order to pave the way for colonization by reducing the strength of an epithelial innate immune defence reaction and also preventing inflammation in the mucosa that factors like VCC can evoke.

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  • 41.
    Blomberg, Jeanette
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Tasselius, Viktor
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Biostatistics, School of Public Health and Community Medicine, Gothenburg University, Gothenburg, Sweden.
    Vergara, Alexander
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Karamat, Fazeelat
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Imran, Qari Muhammad
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Strand, Åsa
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysiologisk botanik. Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC).
    Rosvall, Martin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Björklund, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Pseudomonas syringae infectivity correlates to altered transcript and metabolite levels of Arabidopsis mediator mutants2024Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 14, nr 1, artikel-id 6771Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rapid metabolic responses to pathogens are essential for plant survival and depend on numerous transcription factors. Mediator is the major transcriptional co-regulator for integration and transmission of signals from transcriptional regulators to RNA polymerase II. Using four Arabidopsis Mediator mutants, med16, med18, med25 and cdk8, we studied how differences in regulation of their transcript and metabolite levels correlate to their responses to Pseudomonas syringae infection. We found that med16 and cdk8 were susceptible, while med25 showed increased resistance. Glucosinolate, phytoalexin and carbohydrate levels were reduced already before infection in med16 and cdk8, but increased in med25, which also displayed increased benzenoids levels. Early after infection, wild type plants showed reduced glucosinolate and nucleoside levels, but increases in amino acids, benzenoids, oxylipins and the phytoalexin camalexin. The Mediator mutants showed altered levels of these metabolites and in regulation of genes encoding key enzymes for their metabolism. At later stage, mutants displayed defective levels of specific amino acids, carbohydrates, lipids and jasmonates which correlated to their infection response phenotypes. Our results reveal that MED16, MED25 and CDK8 are required for a proper, coordinated transcriptional response of genes which encode enzymes involved in important metabolic pathways for Arabidopsis responses to Pseudomonas syringae infections.

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  • 42. Bockhop, Fabian
    et al.
    Zeldovich, Marina
    Cunitz, Katrin
    Van Praag, Dominique
    van der Vlegel, Marjolein
    Beissbarth, Tim
    Hagmayer, York
    von Steinbuechel, Nicole
    Kondziella, Daniel (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Koskinen, Lars-Owe D. (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
    Sundström, Nina (Medarbetare/bidragsgivare)
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Measurement invariance of six language versions of the post-traumatic stress disorder checklist for DSM-5 in civilians after traumatic brain injury2022Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, nr 1, artikel-id 16571Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Traumatic brain injury (TBI) is frequently associated with neuropsychiatric impairments such as symptoms of post-traumatic stress disorder (PTSD), which can be screened using self-report instruments such as the Post-Traumatic Stress Disorder Checklist for DSM-5 (PCL-5). The current study aims to inspect the factorial validity and cross-linguistic equivalence of the PCL-5 in individuals after TBI with differential severity. Data for six language groups (n ≥ 200; Dutch, English, Finnish, Italian, Norwegian, Spanish) were extracted from the CENTER-TBI study database. Factorial validity of PTSD was evaluated using confirmatory factor analyses (CFA), and compared between four concurrent structural models. A multi-group CFA approach was utilized to investigate the measurement invariance (MI) of the PCL-5 across languages. All structural models showed satisfactory goodness-of-fit with small between-model variation. The original DSM-5 model for PTSD provided solid evidence of MI across the language groups. The current study underlines the validity of the clinical DSM-5 conceptualization of PTSD and demonstrates the comparability of PCL-5 symptom scores between language versions in individuals after TBI. Future studies should apply MI methods to other sociodemographic (e.g., age, gender) and injury-related (e.g., TBI severity) characteristics to improve the monitoring and clinical care of individuals suffering from PTSD symptoms after TBI.

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  • 43.
    Bodén, Stina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Zheng, Rui
    Department of Surgical Sciences, The EpiHub, Uppsala University, Uppsala, Sweden.
    Ribbenstedt, Anton
    Department of Life Sciences, Chalmers University of Technology, Gothenburg, Sweden.
    Landberg, Rikard
    Department of Life Sciences, Chalmers University of Technology, Gothenburg, Sweden.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Vidman, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Gunter, Marc J.
    International Agency for Research On Cancer, Nutrition and Metabolism Section, Lyon Cedex 08, France; Cancer Epidemiology and Prevention Research Unit, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Winkvist, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för hållbar hälsa. Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Brunius, Carl
    Department of Life Sciences, Chalmers University of Technology, Gothenburg, Sweden.
    Dietary patterns, untargeted metabolite profiles and their association with colorectal cancer risk2024Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 14, nr 1, artikel-id 2244Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We investigated data-driven and hypothesis-driven dietary patterns and their association to plasma metabolite profiles and subsequent colorectal cancer (CRC) risk in 680 CRC cases and individually matched controls. Dietary patterns were identified from combined exploratory/confirmatory factor analysis. We assessed association to LC–MS metabolic profiles by random forest regression and to CRC risk by multivariable conditional logistic regression. Principal component analysis was used on metabolite features selected to reflect dietary exposures. Component scores were associated to CRC risk and dietary exposures using partial Spearman correlation. We identified 12 data-driven dietary patterns, of which a breakfast food pattern showed an inverse association with CRC risk (OR per standard deviation increase 0.89, 95% CI 0.80–1.00, p = 0.04). This pattern was also inversely associated with risk of distal colon cancer (0.75, 0.61–0.96, p = 0.01) and was more pronounced in women (0.69, 0.49–0.96, p = 0.03). Associations between meat, fast-food, fruit soup/rice patterns and CRC risk were modified by tumor location in women. Alcohol as well as fruit and vegetables associated with metabolite profiles (Q2 0.22 and 0.26, respectively). One metabolite reflecting alcohol intake associated with increased CRC risk, whereas three metabolites reflecting fiber, wholegrain, and fruit and vegetables associated with decreased CRC risk.

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  • 44.
    Bokhari, Ahmad H.
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Berggren, Martin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Noreland, Daniel
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap. The Forestry Research Institute of Sweden (Skogforsk), Uppsala Science Park, Uppsala, Sweden.
    Wadbro, Eddie
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap. Department of Mathematics and Computer Science, Karlstad University, Karlstad, Sweden.
    Loudspeaker cabinet design by topology optimization2023Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 13, nr 1, artikel-id 21248Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Using material distribution-based topology optimization, we optimize the bandpass design of a loudspeaker cabinet targeting low frequencies. The objective is to maximize the loudspeaker’s output power for a single frequency as well as a range of frequencies. To model the loudspeaker’s performance, we combine a linear electromechanical transducer model with a computationally efficient hybrid 2D–3D model for sound propagation. The adjoint variable approach computes the gradients of the objective function with respect to the design variables, and the Method of Moving Asymptotes (MMA) solves the topology optimization problem. To manage intermediate values of the material indicator function, a quadratic penalty is added to the objective function, and a non-linear filter is used to obtain a mesh independent design. By carefully selecting the target frequency range, we can guide the optimization algorithm to successfully generate a loudspeaker design with the required bandpass character. To the best of our knowledge, this study constitutes the first successful attempt to design the interior structure of a loudspeaker cabinet using topology optimization.

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  • 45.
    Bokhari, Ahmad Hasnain
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Berggren, Martin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    Noreland, Daniel
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap. The Forestry Research Institute of Sweden (Skogforsk), Uppsala Science Park, Uppsala, Sweden.
    Wadbro, Eddie
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för datavetenskap.
    A computationally efficient hybrid 2D–3D subwoofer model2021Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, artikel-id 255Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A subwoofer generates the lowest frequency range in loudspeaker systems. Subwoofers are used in audio systems for live concerts, movie theatres, home theatres, gaming consoles, cars, etc. During the last decades, numerical simulations have emerged as a cost- and time-efficient complement to traditional experiments in the design process of different products. The aim of this study is to reduce the computational time of simulating the average response for a given subwoofer design. To this end, we propose a hybrid 2D–3D model that reduces the computational time significantly compared to a full 3D model. The hybrid model describes the interaction between different subwoofer components as interacting modules whose acoustic properties can partly be pre-computed. This allows us to efficiently compute the performance of different subwoofer design layouts. The results of the hybrid model are validated against both a lumped element model and a full 3D model over a frequency band of interest. The hybrid model is found to be both accurate and computationally efficient.

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  • 46. Boyero, Luz
    et al.
    Graca, Manuel A. S.
    Tonin, Alan M.
    Perez, Javier
    Swafford, Andrew J.
    Ferreira, Veronica
    Landeira-Dabarca, Andrea
    Alexandrou, Markos A.
    Gessner, Mark O.
    Mckie, Brendan G.
    Albarino, Ricardo J.
    Barmuta, Leon A.
    Callisto, Marcos
    Chara, Julian
    Chauvet, Eric
    Colon-Gaud, Checo
    Dudgeon, David
    Encalada, Andrea C.
    Figueroa, Ricardo
    Flecker, Alexander S.
    Fleituch, Tadeusz
    Frainer, André
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för ekologi, miljö och geovetenskap. Department of Arctic and Marine Biology, UiT The Arctic University of Norway, Tromsø, Norway.
    Goncalves, Jose F., Jr.
    Helson, Julie E.
    Iwata, Tomoya
    Mathooko, Jude
    M'Erimba, Charles
    Pringle, Catherine M.
    Ramirez, Alonso
    Swan, Christopher M.
    Yule, Catherine M.
    Pearson, Richard G.
    Riparian plant litter quality increases with latitude2017Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 7, artikel-id 10562Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Plant litter represents a major basal resource in streams, where its decomposition is partly regulated by litter traits. Litter-trait variation may determine the latitudinal gradient in decomposition in streams, which is mainly microbial in the tropics and detritivore-mediated at high latitudes. However, this hypothesis remains untested, as we lack information on large-scale trait variation for riparian litter. Variation cannot easily be inferred from existing leaf-trait databases, since nutrient resorption can cause traits of litter and green leaves to diverge. Here we present the first global-scale assessment of riparian litter quality by determining latitudinal variation (spanning 107 degrees) in litter traits (nutrient concentrations; physical and chemical defences) of 151 species from 24 regions and their relationships with environmental factors and phylogeny. We hypothesized that litter quality would increase with latitude (despite variation within regions) and traits would be correlated to produce 'syndromes' resulting from phylogeny and environmental variation. We found lower litter quality and higher nitrogen: phosphorus ratios in the tropics. Traits were linked but showed no phylogenetic signal, suggesting that syndromes were environmentally determined. Poorer litter quality and greater phosphorus limitation towards the equator may restrict detritivore-mediated decomposition, contributing to the predominance of microbial decomposers in tropical streams.

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  • 47.
    Brackin, Richard
    et al.
    Queensland, QLD, 4072, Australia.
    Näsholm, Torgny
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Umeå Plant Science Centre (UPSC). Department of Forest Ecology and Management, Swedish University of Agricultural Sciences, SE-901 83 Umeå, Sweden.
    Robinson, Nicole
    School of Agriculture and Food Sciences, The University of Queensland, QLD, 4072, Australia.
    Guillou, Stephane
    School of Agriculture and Food Sciences, The University of Queensland, QLD, 4072, Australia.
    Vinall, Kerry
    School of Agriculture and Food Sciences, The University of Queensland, QLD, 4072, Australia.
    Lakshmanan, Prakash
    Sugar Research Australia, 50 Meiers Road, Indooroopilly, QLD 4068, Australia.
    Schmidt, Susanne
    School of Agriculture and Food Sciences, The University of Queensland, QLD, 4072, Australia.
    Inselsbacher, Erich
    Department of Forest Ecology and Management, Swedish University of Agricultural Sciences, SE-901 83 Umeå, Sweden; University of Vienna, Department of Geography and Regional Research, Vienna, AT-1090, Austria.
    Nitrogen fluxes at the root-soil interface show a mismatch of nitrogen fertilizer supply and sugarcane root uptake capacity2015Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 5, artikel-id 15727Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Globally only approximate to 50% of applied nitrogen (N) fertilizer is captured by crops, and the remainder can cause pollution via runoff and gaseous emissions. Synchronizing soil N supply and crop demand will address this problem, however current soil analysis methods provide little insight into delivery and acquisition of N forms by roots. We used microdialysis, a novel technique for in situ quantification of soil nutrient fluxes, to measure N fluxes in sugarcane cropping soils receiving different fertilizer regimes, and compare these with N uptake capacities of sugarcane roots. We show that in fertilized sugarcane soils, fluxes of inorganic N exceed the uptake capacities of sugarcane roots by several orders of magnitude. Contrary, fluxes of organic N closely matched roots' uptake capacity. These results indicate root uptake capacity constrains plant acquisition of inorganic N. This mismatch between soil N supply and root N uptake capacity is a likely key driver for low N efficiency in the studied crop system. Our results also suggest that (i) the relative contribution of inorganic N for plant nutrition may be overestimated when relying on soil extracts as indicators for root-available N, and (ii) organic N may contribute more to crop N supply than is currently assumed.

  • 48.
    Brynolfsson, Patrik
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Nilsson, David
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Torheim, Turid
    Asklund, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Thellenberg Karlsson, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Trygg, Johan
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Nyholm, Tufve
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Garpebring, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Haralick texture features from apparent diffusion coefficient (ADC) MRI images depend on imaging and pre-processing parameters2017Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 7, artikel-id 4041Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In recent years, texture analysis of medical images has become increasingly popular in studies investigating diagnosis, classification and treatment response assessment of cancerous disease. Despite numerous applications in oncology and medical imaging in general, there is no consensus regarding texture analysis workflow, or reporting of parameter settings crucial for replication of results. The aim of this study was to assess how sensitive Haralick texture features of apparent diffusion coefficient (ADC) MR images are to changes in five parameters related to image acquisition and pre-processing: noise, resolution, how the ADC map is constructed, the choice of quantization method, and the number of gray levels in the quantized image. We found that noise, resolution, choice of quantization method and the number of gray levels in the quantized images had a significant influence on most texture features, and that the effect size varied between different features. Different methods for constructing the ADC maps did not have an impact on any texture feature. Based on our results, we recommend using images with similar resolutions and noise levels, using one quantization method, and the same number of gray levels in all quantized images, to make meaningful comparisons of texture feature results between different subjects.

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  • 49. Bäckman, Lars
    et al.
    Waris, Otto
    Johansson, Jarkko
    Andersson, Micael
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Rinne, Juha O.
    Alakurtti, Kati
    Soveri, Anna
    Laine, Matti
    Nyberg, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper. Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Increased dopamine release after working-memory updating training: Neurochemical correlates of transfer2017Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 7, artikel-id 7160Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Previous work demonstrates that working-memory (WM) updating training results in improved performance on a letter-memory criterion task, transfers to an untrained n-back task, and increases striatal dopamine (DA) activity during the criterion task. Here, we sought to replicate and extend these findings by also examining neurochemical correlates of transfer. Four positron emission tomography (PET) scans using the radioligand raclopride were performed. Two of these assessed DAD2 binding (letter memory; n-back) before 5 weeks of updating training, and the same two scans were performed post training. Key findings were (a) pronounced training-related behavioral gains in the lettermemory criterion task, (b) altered striatal DAD2 binding potential after training during letter-memory performance, suggesting training-induced increases in DA release, and (c) increased striatal DA activity also during the n-back transfer task after the intervention, but no concomitant behavioral transfer. The fact that the training-related DA alterations during the transfer task were not accompanied by behavioral transfer suggests that increased DA release may be a necessary, but not sufficient, condition for behavioral transfer to occur.

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  • 50.
    Bóta, András
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik. Embedded Intelligent Systems Lab, Department of Computer Science, Electrical and Space Engineering, Luleå University of Technology, Luleå, Sweden.
    Holmberg, Martin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Gardner, Lauren
    Department of Civil and Systems Engineering, Johns Hopkins University, MD, Baltimore, United States.
    Rosvall, Martin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    Socioeconomic and environmental patterns behind H1N1 spreading in Sweden2021Ingår i: Scientific Reports, E-ISSN 2045-2322, Vol. 11, nr 1, artikel-id 22512Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Identifying the critical factors related to influenza spreading is crucial in predicting and mitigating epidemics. Specifically, uncovering the relationship between epidemic onset and various risk indicators such as socioeconomic, mobility and climate factors can reveal locations and travel patterns that play critical roles in furthering an outbreak. We study the 2009 A(H1N1) influenza outbreaks in Sweden’s municipalities between 2009 and 2015 and use the Generalized Inverse Infection Method (GIIM) to assess the most significant contributing risk factors. GIIM represents an epidemic spreading process on a network: nodes correspond to geographical objects, links indicate travel routes, and transmission probabilities assigned to the links guide the infection process. Our results reinforce existing observations that the influenza outbreaks considered in this study were driven by the country’s largest population centers, while meteorological factors also contributed significantly. Travel and other socioeconomic indicators have a negligible effect. We also demonstrate that by training our model on the 2009 outbreak, we can predict the epidemic onsets in the following five seasons with high accuracy.

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