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Sökning: WFRF:(Granberg Fredrik)

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3.
  • Ail, Ujwala, et al. (författare)
  • Room temperature synthesis of transition metal silicide-conducting polymer micro-composites for thermoelectric applications
  • 2017
  • Ingår i: Synthetic metals. - : Elsevier BV. - 0379-6779 .- 1879-3290. ; 225, s. 55-63
  • Tidskriftsartikel (refereegranskat)abstract
    • Organic polymer thermoelectrics (TE) as well as transition metal (TM) silicides are two thermoelectric class of materials of interest because they are composed of atomic elements of high abundance; which is a prerequisite for mass implementation of thermoelectric (TE) solutions for solar and waste heat recovery. But both materials have drawbacks when it comes to finding low-cost manufacturing. The metal silicide needs high temperature (>1000 °C) for creating TE legs in a device from solid powder, but it is easy to achieve long TE legs in this case. On the contrary, organic TEs are synthesized at low temperature from solution. However, it is difficult to form long legs or thick films because of their low solubility. In this work, we propose a novel method for the room temperature synthesis of TE composite containing the microparticles of chromium disilicide; CrSi2 (inorganic filler) in an organic matrix of nanofibrillated cellulose- poly(3,4-ethyelenedioxythiophene)-polystyrene sulfonate (NFC-PEDOT:PSS). With this method, it is easy to create long TE legs in a room temperature process. The originality of the approach is the use of conducting polymer aerogel microparticles mixed with CrSi2 microparticles to obtain a composite solid at room temperature under pressure. We foresee that the method can be scaled up to fabricate and pattern TE modules. The composite has an electrical conductivity (σ) of 5.4 ± 0.5 S/cm and the Seebeck coefficient (α) of 88 ± 9 ΌV/K, power factor (α2σ) of 4 ± 1 ΌWm−1K−2 at room temperature. At a temperature difference of 32 °C, the output power/unit area drawn across the load, with the resistance same as the internal resistance of the device is 0.6 ± 0.1 ΌW/cm2.
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4.
  • Andersson-Sköld, Yvonne, et al. (författare)
  • An integrated method for assessing climate-related risks and adaptation alternatives in urban areas
  • 2015
  • Ingår i: Climate Risk Management. - : Elsevier BV. - 2212-0963. ; 7, s. 31-50
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2015 The Authors. The urban environment is a complex structure with interlinked social, ecological and technical structures. Global warming is expected to have a broad variety of impacts, which will add to the complexity. Climate changes will force adaptation, to reduce climate-related risks. Adaptation measures can address one aspect at the time, or aim for a holistic approach to avoid maladaptation. This paper presents a systematic, integrated approach for assessing alternatives for reducing the risks of heat waves, flooding and air pollution in urban settings, with the aim of reducing the risk of maladaptation. The study includes strategies covering different spatial scales, and both the current climate situation and the climate predicted under climate change scenarios. The adaptation strategies investigated included increasing vegetation; selecting density, height and colour of buildings; and retreat or resist (defend) against sea-level rise. Their effectiveness was assessed with regard to not only flooding, heat stress and air quality but also with regard to resource use, emissions to air (incl. GHG), soil and water, and people's perceptions and vulnerability. The effectiveness of the strategies were ranked on a common scale (from -3 to 3) in an integrated assessment. Integrated assessments are recommended, as they help identify the most sustainable solutions, but to reduce the risk of maladaptation they require experts from a variety of disciplines. The most generally applicable recommendation, derived from the integrated assessment here, taking into account both expertise from different municipal departments, literature surveys, life cycle assessments and publics perceptions, is to increase the urban greenery, as it contributes to several positive aspects such as heat stress mitigation, air quality improvement, effective storm-water and flood-risk management, and it has several positive social impacts. The most favourable alternative was compact, mid-rise, light coloured building design with large parks/green areas and trees near buildings.
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5.
  • Belak, Sandor, et al. (författare)
  • High-throughput sequencing in veterinary infection biology and diagnostics
  • 2013
  • Ingår i: Revue Scientifique et Technique- Office International des Epizooties. - 0253-1933 .- 1608-0637. ; 32, s. 893-915
  • Tidskriftsartikel (refereegranskat)abstract
    • Sequencing methods have improved rapidly since the first versions of the Sanger techniques, facilitating the development of very powerful tools for detecting and identifying various pathogens, such as viruses, bacteria and other microbes. The ongoing development of high-throughput sequencing (HTS; also known as next-generation sequencing) technologies has resulted in a dramatic reduction in DNA sequencing costs, making the technology more accessible to the average laboratory. In this White Paper of the World Organisation for Animal Health (0IE) Collaborating Centre for the Biotechnology-based Diagnosis of Infectious Diseases in Veterinary Medicine (Uppsala, Sweden), several approaches and examples of HTS are summarised, and their diagnostic applicability is briefly discussed. Selected future aspects of HTS are outlined, including the need for bioinformatic resources, with a focus on improving the diagnosis and control of infectious diseases in veterinary medicine.
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6.
  • Belak, Sandor, et al. (författare)
  • New viruses in veterinary medicine, detected by metagenomic approaches
  • 2013
  • Ingår i: Veterinary Microbiology. - : Elsevier BV. - 0378-1135 .- 1873-2542. ; 165, s. 95-101
  • Tidskriftsartikel (refereegranskat)abstract
    • In our world, which is faced today with exceptional environmental changes and dramatically intensifying globalisation, we are encountering challenges due to many new factors, including the emergence or re-emergence of novel, so far “unknown” infectious diseases. Although a broad arsenal of diagnostic methods is at our disposal, the majority of the conventional diagnostic tests is highly virus-specific or is targeted entirely towards a limited group of infectious agents. This specificity complicates or even hinders the detection of new or unexpected pathogens, such as new, emerging or re-emerging viruses or novel viral variants. The recently developed approaches of viral metagenomics provide an effective novel way to screen samples and detect viruses without previous knowledge of the infectious agent, thereby enabling a better diagnosis and disease control, in line with the “One World, One Health” principles (www.oneworldonehealth.org). Using metagenomic approaches, we have recently identified a broad variety of new viruses, such as novel bocaviruses, Torque Teno viruses, astroviruses, rotaviruses and kobuviruses in porcine disease syndromes, new virus variants in honeybee populations, as well as a range of other infectious agents in further host species. These findings indicate that the metagenomic detection of viral pathogens is becoming now a powerful, cultivation-independent, and useful novel diagnostic tool in veterinary diagnostic virology.
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7.
  • Belak, Sandor, et al. (författare)
  • Next-Generation Sequencing in Veterinary Medicine: How Can the Massive Amount of Information Arising from High-Throughput Technologies Improve Diagnosis, Control, and Management of Infectious Diseases?
  • 2015
  • Ingår i: Veterinary Infection Biology: Molecular Diagnostics and High-Throughput Strategies. - New York, NY : Springer New York. - 9781493920037 ; 1247:1247, s. 415-436
  • Bokkapitel (refereegranskat)abstract
    • The development of high-throughput molecular technologies and associated bioinformatics has dramatically changed the capacities of scientists to produce, handle, and analyze large amounts of genomic, transcriptomic, and proteomic data. A clear example of this step-change is represented by the amount of DNA sequence data that can be now produced using next-generation sequencing (NGS) platforms. Similarly, recent improvements in protein and peptide separation efficiencies and highly accurate mass spectrometry have promoted the identification and quantification of proteins in a given sample. These advancements in biotechnology have increasingly been applied to the study of animal infectious diseases and are beginning to revolutionize the way that biological and evolutionary processes can be studied at the molecular level. Studies have demonstrated the value of NGS technologies for molecular characterization, ranging from metagenomic characterization of unknown pathogens or microbial communities to molecular epidemiology and evolution of viral quasispecies. Moreover, high-throughput technologies now allow detailed studies of host-pathogen interactions at the level of their genomes (genomics), transcriptomes (transcriptomics), or proteomes (proteomics). Ultimately, the interaction between pathogen and host biological networks can be questioned by analytically integrating these levels (integrative OMICS and systems biology). The application of high-throughput biotechnology platforms in these fields and their typical low-cost per information content has revolutionized the resolution with which these processes can now be studied.The aim of this chapter is to provide a current and prospective view on the opportunities and challenges associated with the application of massive parallel sequencing technologies to veterinary medicine, with particular focus on applications that have a potential impact on disease control and management.
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  • Berglund, Eva C., et al. (författare)
  • Genome dynamics of Bartonella grahamii in micro-populations of woodland rodents
  • 2010
  • Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 11, s. 152-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Rodents represent a high-risk reservoir for the emergence of new human pathogens. The recent completion of the 2.3 Mb genome of Bartonella grahamii, one of the most prevalent blood-borne bacteria in wild rodents, revealed a higher abundance of genes for host-cell interaction systems than in the genomes of closely related human pathogens. The sequence variability within the global B. grahamii population was recently investigated by multi locus sequence typing, but no study on the variability of putative host-cell interaction systems has been performed. Results: To study the population dynamics of B. grahamii, we analyzed the genomic diversity on a whole-genome scale of 27 B. grahamii strains isolated from four different species of wild rodents in three geographic locations separated by less than 30 km. Even using highly variable spacer regions, only 3 sequence types were identified. This low sequence diversity contrasted with a high variability in genome content. Microarray comparative genome hybridizations identified genes for outer surface proteins, including a repeated region containing the fha gene for filamentous hemaggluttinin and a plasmid that encodes a type IV secretion system, as the most variable. The estimated generation times in liquid culture medium for a subset of strains ranged from 5 to 22 hours, but did not correlate with sequence type or presence/absence patterns of the fha gene or the plasmid. Conclusion: Our study has revealed a geographic microstructure of B. grahamii in wild rodents. Despite near-identity in nucleotide sequence, major differences were observed in gene presence/absence patterns that did not segregate with host species. This suggests that genetically similar strains can infect a range of different hosts.
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10.
  • Berglund, Eva C., et al. (författare)
  • Rapid diversification by recombination in Bartonella grahamii from wild rodents in Asia contrasts with low levels of genomic divergence in Northern Europe and America
  • 2010
  • Ingår i: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 19:11, s. 2241-2255
  • Tidskriftsartikel (refereegranskat)abstract
    • Bartonella is a genus of vector-borne bacteria that infect the red blood cells of mammals, and includes several human-specific and zoonotic pathogens. Bartonella grahamii has a wide host range and is one of the most prevalent Bartonella species in wild rodents. We studied the population structure, genome content and genome plasticity of a collection of 26 B. grahamii isolates from 11 species of wild rodents in seven countries. We found strong geographic patterns, high recombination frequencies and large variations in genome size in B. grahamii compared with previously analysed cat- and human-associated Bartonella species. The extent of sequence divergence in B. grahamii populations was markedly lower in Europe and North America than in Asia, and several recombination events were predicted between the Asian strains. We discuss environmental and demographic factors that may underlie the observed differences.
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11.
  • Berglund, Eva C., et al. (författare)
  • Run-off replication of host-adaptability genes is associated with gene transfer agents in the genome of mouse-infecting Bartonella grahamii
  • 2009
  • Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 5:7, s. e1000546-
  • Tidskriftsartikel (refereegranskat)abstract
    • The genus Bartonella comprises facultative intracellular bacteria adapted to mammals, including previously recognized and emerging human pathogens. We report the 2,341,328 bp genome sequence of Bartonella grahamii, one of the most prevalent Bartonella species in wild rodents. Comparative genomics revealed that rodent-associated Bartonella species have higher copy numbers of genes for putative host-adaptability factors than the related human-specific pathogens. Many of these gene clusters are located in a highly dynamic region of 461 kb. Using hybridization to a microarray designed for the B. grahamii genome, we observed a massive, putatively phage-derived run-off replication of this region. We also identified a novel gene transfer agent, which packages the bacterial genome, with an over-representation of the amplified DNA, in 14 kb pieces. This is the first observation associating the products of run-off replication with a gene transfer agent. Because of the high concentration of gene clusters for host-adaptation proteins in the amplified region, and since the genes encoding the gene transfer agent and the phage origin are well conserved in Bartonella, we hypothesize that these systems are driven by selection. We propose that the coupling of run-off replication with gene transfer agents promotes diversification and rapid spread of host-adaptability factors, facilitating host shifts in Bartonella.
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  • Böhlenius, Henrik, et al. (författare)
  • Biomass production and fuel characteristics from long rotation poplar plantations
  • 2023
  • Ingår i: Biomass and Bioenergy. - : Elsevier Ltd. - 0961-9534 .- 1873-2909. ; 178
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the key elements in this transition is the securing of a large supply of sustainable biomass. In this study, the feedstock potential of long rotation poplar plantations (12–30 years with diameter of 15 of 30 cm) was determined and the properties of poplar biomass fuel were analyzed with the aim of using thermochemical conversion methods to produce biofuel. Our results demonstrate that Sweden has great potential for producing biofuels from long rotation poplar plantations, with a total of 1.8 million hectares (ha) consisting of arable (0.5 million ha) and forested arable land (1.3 million ha). Based on available land and biomass production potential, our results indicate that 10 million Mg DW could be produced annually. Regions in mid/southern Sweden have the largest potential (larger areas and higher biomass production. Our results further suggest that poplar biomass from these plantations has fuel characteristics similar to forest fuels from other conifer tree species, making the biomass suitable as feedstock for biofuel production based on thermochemical conversion methods. If 25% of the available land were used, 7.6 TWh methanol biofuels could be produced annually from 16 biofuel plants, using 160,000 Mg DW yr−1, primarily located in the southern part of Sweden. Two counties (Skåne and Västra Götaland) would be able to support their biofuel plants using poplar plantations as feedstock. Stable biofuel production in the other counties would depend on collaborating with neighboring counties.
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14.
  • Casar Borota, Olivera, et al. (författare)
  • Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas : Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.
  • 2017
  • Ingår i: American Journal of Surgical Pathology. - 0147-5185 .- 1532-0979. ; 41:9, s. 1238-1246
  • Tidskriftsartikel (refereegranskat)abstract
    • Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.
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15.
  • Crona, Joakim, et al. (författare)
  • Metastases from Neuroendocrine Tumors to the Breast Are More Common than Previously Thought. A Diagnostic Pitfall?
  • 2013
  • Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 0364-2313 .- 1432-2323. ; 37:7, s. 1701-1706
  • Tidskriftsartikel (refereegranskat)abstract
    • Metastases from neuroendocrine tumors (NETs) to the breast have been described as a rare phenomenon. Presentation, imaging results, and cytopathologic findings of these tumours may closely mimic those of a mammary carcinoma. This study was a retrospective review of 661 patients with metastatic NETs, of whom 280 were females, treated at Uppsala University Hospital, Uppsala, Sweden. Patients with pathological breast lesions were identified. Histopathological slides from available NET breast lesions were analyzed for mammary carcinoma and neuroendocrine markers. We have identified 20 female patients with NET metastases to the breast, 11/235 with small intestinal NETs, 8/55 with lung NETs, and 1/6 with thymic NETs. There were no male patients with NET metastatic to the breast. Four patients had their breast lesion initially diagnosed as mammary carcinoma. Retrospectively, these lesions showed negative staining for mammary carcinoma markers. Metastases to the breast from neuroendocrine tumors may be more common than previously thought. Patients with a lesion to the breast and symptoms typical for NET may benefit from additional histopathological investigation, because NET metastases and mammary carcinoma have different immunohistochemical profiles.
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16.
  • Engel, Philipp, et al. (författare)
  • The Bee Microbiome: Impact on Bee Health and Model for Evolution and Ecology of Host-Microbe Interactions
  • 2016
  • Ingår i: mBio. - : American Society for Microbiology. - 2161-2129 .- 2150-7511. ; 7:2
  • Forskningsöversikt (refereegranskat)abstract
    • As pollinators, bees are cornerstones for terrestrial ecosystem stability and key components in agricultural productivity. All animals, including bees, are associated with a diverse community of microbes, commonly referred to as the micro biome. The bee micro biome is likely to be a crucial factor affecting host health. However, with the exception of a few pathogens, the impacts of most members of the bee microbiome on host health are poorly understood. Further, the evolutionary and ecological forces that shape and change the microbiome are unclear. Here, we discuss recent progress in our understanding of the bee microbiome, and we present challenges associated with its investigation. We conclude that global coordination of research efforts is needed to fully understand the complex and highly dynamic nature of the interplay between the bee micro biome, its host, and the environment. High-throughput sequencing technologies are ideal for exploring complex biological systems, including host-microbe interactions. To maximize their value and to improve assessment of the factors affecting bee health, sequence data should be archived, curated, and analyzed in ways that promote the synthesis of different studies. To this end, the BeeBiome consortium aims to develop an online database which would provide reference sequences, archive metadata, and host analytical resources. The goal would be to support applied and fundamental research on bees and their associated microbes and to provide a collaborative framework for sharing primary data from different research programs, thus furthering our understanding of the bee microbiome and its impact on pollinator health.
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  • Granberg, Fredrik, et al. (författare)
  • Adenovirus-induced alterations in host cell gene expression prior to the onset of viral gene expression
  • 2006
  • Ingår i: Virology. - : Elsevier BV. - 0042-6822 .- 1096-0341. ; 353:1, s. 1-5
  • Tidskriftsartikel (refereegranskat)abstract
    • In this report, we have studied gene expression profiles in human primary lung fibroblasts (IMR-90) during the very early phase of an adenovirus infection. Eight out of twelve genes with known functions encoded transcription factors linked to two major cellular processes; inhibition of cell growth (ATF3, ATF4, KLF4, KLF6 and ELK3) and immune response (NR4A1 and CEBPB), indicating that the earliest consequences of an adenovirus infection are growth arrest and induction of an immune response. A time course analysis showed that the induction of these immediate-early response genes was transient and suppressed after the onset of the adenovirus early gene expression.
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19.
  • Granberg, Fredrik, et al. (författare)
  • Complete Genome Sequence of an African Swine Fever Virus Isolate from Sardinia, Italy
  • 2016
  • Ingår i: Microbiology Resource Announcements. - 2576-098X. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous genetic characterization of African swine fever virus isolates from the Italian island of Sardinia, where the virus has been present since 1978, has largely been limited to a few selected genomic regions. Here, we report the complete genome sequence of the isolate 47/Ss/08 collected during an outbreak in 2008.
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20.
  • Granberg, Fredrik, 1975- (författare)
  • Global Profiling of Host Cell Gene Expression During Adenovirus Infection
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • To investigate mechanisms involved in virus-host interactions, global changes in host gene expression were examined during infection with adenovirus type 2 (Ad2) using cDNA microarray technology. In paper I and II, transcriptional changes in HeLa cells were investigated during the early and late phase of infection, respectively. A limited number of genes, mainly implicated in cell growth and antiviral defence, were found to be differentially expressed in the early phase, whereas modulation of host cell gene expression during the late phase was augmented and mainly focused on growth inhibition and cell architecture. The experimental set-up was then redesigned to follow transcriptional regulatory events in growth synchronised, human primary lung fibroblasts. The immediate response of the host cell within two hours of infection was investigated in paper III, revealing a transient induction of a small number of cellular alert genes. This was followed by an expanded time course presented in paper IV, which included gene expression profiling at eight consecutive time points throughout the infectious cycle. The results indicated that specific sets of cellular genes were targeted at different stages of the infection, and four distinct periods were identified. In summary, the studies presented in this thesis demonstrate that adenovirus interferes with many cellular processes during the progression of infection to optimize the cellular environment for viral replication. These include cell cycle control, cell growth and growth inhibition, as well as DNA, RNA and protein metabolism. However, a transient induction of cellular genes involved in immune response and growth inhibition was observed before the onset of viral gene expression. During the very late stages of infection, the expression of a large number of genes involved in maintaining the cell structure was down-regulated, presumably to facilitate the spread of progeny virus.
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21.
  • Granberg, Fredrik, et al. (författare)
  • Metagenomic approaches to disclose disease-associated pathogens: detection of viral pathogens in honeybees
  • 2015
  • Ingår i: Veterinary infection biology: molecular diagnostics and high-throughput strategies Methods in Molecular Biology. - New York, NY : Springer New York. - 9781493920044 ; 1247:1247, s. 491-511
  • Bokkapitel (refereegranskat)abstract
    • Metagenomic approaches have become invaluable for culture-independent and sequence-independent detection and characterization of disease-associated pathogens. Here, the sequential steps from sampling to verification of results are described for a metagenomic-based approach to detect potential pathogens in honeybees. The pre-sequencing steps are given in detail, but due to the rapid development of sequencing technologies, all platform-specific procedures, as well as subsequent bioinformatics analysis, are more generally described. It should also be noted that this approach could, with minor modifications, be adapted for other organisms and sample matrices.
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22.
  • Granberg, Fredrik, et al. (författare)
  • Metagenomic Detection of Viral Pathogens in Spanish Honeybees: Co- Infection by Aphid Lethal Paralysis, Israel Acute Paralysis and Lake Sinai Viruses
  • 2013
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The situation in Europe concerning honeybees has in recent years become increasingly aggravated with steady decline in populations and/or catastrophic winter losses. This has largely been attributed to the occurrence of a variety of known and "unknown", emerging novel diseases. Previous studies have demonstrated that colonies often can harbour more than one pathogen, making identification of etiological agents with classical methods difficult. By employing an unbiased metagenomic approach, which allows the detection of both unexpected and previously unknown infectious agents, the detection of three viruses, Aphid Lethal Paralysis Virus (ALPV), Israel Acute Paralysis Virus (IAPV), and Lake Sinai Virus (LSV), in honeybees from Spain is reported in this article. The existence of a subgroup of ALPV with the ability to infect bees was only recently reported and this is the first identification of such a strain in Europe. Similarly, LSV appear to be a still unclassified group of viruses with unclear impact on colony health and these viruses have not previously been identified outside of the United States. Furthermore, our study also reveals that these bees carried a plant virus, Turnip Ringspot Virus (TuRSV), potentially serving as important vector organisms. Taken together, these results demonstrate the new possibilities opened up by high-throughput sequencing and metagenomic analysis to study emerging new diseases in domestic and wild animal populations, including honeybees.
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23.
  • Granberg, Fredrik, et al. (författare)
  • Modulation of host cell gene expression during onset of the late phase of an adenovirus infection is focused on growth inhibition and cell architecture.
  • 2005
  • Ingår i: Virology. - 0042-6822. ; 343:2, s. 236-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Microarray analysis of host cell gene expression during an adenovirus type 2 infection showed that the number of regulated genes, as well as the magnitude of change, was increased as the infection proceeded into the late phase. In contrast to the early phase of infection when the majority of differentially expressed genes were upregulated, expression of most of the regulated genes (82 out of 112) declined during the late phase. In particular, numerous TGF-beta inducible genes and several TGF-beta-independent growth-arrest-inducing genes were targeted. Of the 30 genes upregulated more than 2-fold at 20 h post-infection, nearly two-thirds of encoded proteins are involved in cell metabolism. The data indicate that adenovirus primarily targets cellular genes involved in antiviral defense, cell growth arrest and apoptosis, as well as cell metabolism, to ensure sufficient production of viral progeny.
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24.
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25.
  • Granberg, Fredrik, et al. (författare)
  • Molecular approaches to recognize relevant and emerging infectious diseases in animals
  • 2015
  • Ingår i: Veterinary Infection Biology: Molecular Diagnostics and High-Throughput Strategies. - New York, NY : Springer New York. - 9781493920037 ; 1247, s. 109-124
  • Bokkapitel (refereegranskat)abstract
    • Since the introduction of the first molecular tests, there has been a continuous effort to develop new and improved assays for rapid and efficient detection of infectious agents. This has been motivated by a need for improved sensitivity as well as results that can be easily communicated. The experiences and knowledge gained at theWorld Organisation for Animal Health(OIE)Collaborating Centre for Biotechnology-based Diagnosis of Infectious Diseases in Veterinary Medicine, Uppsala, Sweden, will here be used to provide an overview of the different molecular approaches that can be used to diagnose and identify relevant and emerging infectious diseases in animals.
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26.
  • Granberg, Fredrik (författare)
  • Next-generation sequencing workflows in veterinary infection biology: towards validation and quality assurance
  • 2016
  • Ingår i: Revue Scientifique et Technique- Office International des Epizooties. - : O.I.E (World Organisation for Animal Health). - 0253-1933 .- 1608-0637. ; 35, s. 67-81
  • Forskningsöversikt (refereegranskat)abstract
    • Recent advancements in DNA sequencing methodologies and sequence data analysis have revolutionised research in many areas of biology and medicine, including veterinary infection biology. New technology is poised to bridge the gap between the research and diagnostic laboratory. This paper defines the potential diagnostic value and purposes of next-generation sequencing (NGS) applications in veterinary infection biology and explores their compatibility with the existing validation principles and methods of the World Organisation for Animal Health. Critical parameters for validation and quality control (quality metrics) are suggested, with reference to established validation and quality assurance guidelines for NGS-based methods of diagnosing human heritable diseases. Although most currently described NGS applications in veterinary infection biology are not primary diagnostic tests that directly result in control measures, this critical reflection on the advantages and remaining challenges of NGS technology should stimulate discussion on its diagnostic value and on the potential to validate NGS methods and monitor their diagnostic performance.
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27.
  • Granberg, Fredrik (författare)
  • No evidence of enteric viral involvement in the new neonatal porcine diarrhoea syndrome in Danish pigs
  • 2017
  • Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this study was to investigate whether the syndrome New Neonatal Porcine Diarrhoea Syndrome (NNPDS) is associated with a viral aetiology. Four well-managed herds experiencing neonatal diarrhoea and suspected to be affected by NNPDS were included in a case-control set up. A total of 989 piglets were clinically examined on a daily basis. Samples from diarrhoeic and non-diarrhoeic piglets at the age of three to seven days were selected for extensive virological examination using specific real time polymerase chain reactions (qPCRs) and general virus detection methods.Results: A total of 91.7% of the animals tested positive by reverse transcription qPCR (RT-qPCR) for porcine kobuvirus 1 (PKV-1) while 9% and 3% were found to be positive for rotavirus A and porcine teschovirus (PTV), respectively. The overall prevalence of porcine astrovirus (PAstV) was 75% with 69.8% of the PAstV positive pigs infected with PAstV type 3. No animals tested positive for rotavirus C, coronavirus (TGEV, PEDV and PRCV), sapovirus, enterovirus, parechovirus, saffoldvirus, cosavirus, klassevirus or porcine circovirus type 2 (PCV2). Microarray analyses performed on a total of 18 animals were all negative, as were eight animals examined by Transmission Electron Microscopy (TEM). Using Next Generation de novo sequencing (de novo NGS) on pools of samples from case animals within all herds, PKV-1 was detected in four herds and rotavirus A, rotavirus C and PTV were detected in one herd each.Conclusions: Our detailed analyses of piglets from NNPDS-affected herds demonstrated that viruses did not pose a significant contribution to NNPDS. However, further investigations are needed to investigate if a systemic virus infection plays a role in the pathogenesis of NNPDS.
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28.
  • Granberg, Fredrik, et al. (författare)
  • Novel technologies applied to the nucleotide sequencing and comparative sequence analysis of the genomes of infectious agents in veterinary medicine
  • 2016
  • Ingår i: Revue Scientifique et Technique- Office International des Epizooties. - : O.I.E (World Organisation for Animal Health). - 0253-1933 .- 1608-0637. ; 35, s. 25-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Next-generation sequencing (NGS), also referred to as deep, high-throughput or massively parallel sequencing, is a powerful new tool that can be used for the complex diagnosis and intensive monitoring of infectious disease in veterinary medicine. NGS technologies are also being increasingly used to study the aetiology, genomics, evolution and epidemiology of infectious disease, as well as host-pathogen interactions and other aspects of infection biology.This review briefly summarises recent progress and achievements in this field by first introducing a range of novel techniques and then presenting examples of NGS applications in veterinary infection biology. Various work steps and processes for sampling and sample preparation, sequence analysis and comparative genomics, and improving the accuracy of genomic prediction are discussed, as are bioinformatics requirements. Examples of sequencing-based applications and comparative genomics in veterinary medicine are then provided. This review is based on novel references selected from the literature and on experiences of the World Organisation for Animal Health (OIE) Collaborating Centre for the Biotechnology-based Diagnosis of Infectious Diseases in Veterinary Medicine, Uppsala, Sweden.
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29.
  • Granberg, Hjalmar, et al. (författare)
  • It’s a bird! It’s a plane! It’s a super multimaterial!
  • 2015
  • Ingår i: Paper Conference and Trade Show (PaperCon 2015). - : TAPPI Press. - 9781510818873 ; , s. 492-504
  • Konferensbidrag (refereegranskat)abstract
    • Matching market demands and technological solutions is not always straightforward. In this article, we report on one material, a cellulose-PLA multimaterial, which was made on a full-scale pilot paper machine and adapted to five different market applications having specialized and often conflicting demands. The material can be injection molded, 3D-printed, hot pressed, treated as a textile, used in a laminate, or converted as a paper board, giving it a wide range of possible properties depending on how it is processed.The five application areas presented here were identified as gaps in the marketplace where seemingly conflicting needs were desired: opacity and transparency; compact for transport but having an expanded size during use; stiffness and flexibility; strength and light-weight; and durability and degradability. These properties are exemplified in a number of material and product demonstrators, illustrating how tailored solutions can give products with distinctly different personalities. The material can be made flexible and given movement as graceful as the wing of a bird or be processed to be strong and light-weight enough to be used in vehicles like airplanes. By having one material that is produced on a large scale, but then processed according to specific market demands and expectations, the gap between needing scale and needing scope is bridged.
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30.
  • Granberg, Tobias, et al. (författare)
  • Enlarged perivascular spaces in multiple sclerosis on magnetic resonance imaging : a systematic review and meta-analysis
  • 2020
  • Ingår i: Journal of Neurology. - : Springer. - 0340-5354 .- 1432-1459. ; 267:11, s. 3199-3212
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Perivascular spaces can become detectable on magnetic resonance imaging (MRI) upon enlargement, referred to as enlarged perivascular spaces (EPVS) or Virchow-Robin spaces. EPVS have been linked to small vessel disease. Some studies have also indicated an association of EPVS to neuroinflammation and/or neurodegeneration. However, there is conflicting evidence with regards to their potential as a clinically relevant imaging biomarker in multiple sclerosis (MS).METHODS: To perform a systematic review and meta-analysis of EPVS as visualized by MRI in MS. Nine out of 299 original studies addressing EPVS in humans using MRI were eligible for the systematic review and meta-analysis including a total of 457 MS patients and 352 control subjects.RESULTS: In MS, EPVS have been associated with cognitive decline, contrast-enhancing MRI lesions, and brain atrophy. Yet, these associations were not consistent between studies. The meta-analysis revealed that MS patients have greater EPVS prevalence (odds ratio = 4.61, 95% CI = [1.84; 11.60], p = 0.001) as well as higher EPVS counts (standardized mean difference [SMD] = 0.46, 95% CI = [0.26; 0.67], p < 0.001) and larger volumes (SMD = 0.88, 95% CI = [0.19; 1.56], p = 0.01) compared to controls.CONCLUSIONS: Available literature suggests a higher EPVS burden in MS patients compared to controls. The association of EPVS to neuroinflammatory or -degenerative pathology in MS remains inconsistent. Thus, there is currently insufficient evidence supporting EPVS as diagnostic and/or prognostic marker in MS. In order to benefit future comparisons of studies, we propose recommendations on EPVS assessment standardization in MS. PROSPERO No: CRD42019133946.
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31.
  • Guy, Lionel, et al. (författare)
  • A Gene Transfer Agent and a Dynamic Repertoire of Secretion Systems Hold the Keys to the Explosive Radiation of the Emerging Pathogen Bartonella
  • 2013
  • Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:3, s. e1003393-
  • Tidskriftsartikel (refereegranskat)abstract
    • Gene transfer agents (GTAs) randomly transfer short fragments of a bacterial genome. A novel putative GTA was recently discovered in the mouse-infecting bacterium Bartonella grahamii. Although GTAs are widespread in phylogenetically diverse bacteria, their role in evolution is largely unknown. Here, we present a comparative analysis of 16 Bartonella genomes ranging from 1.4 to 2.6 Mb in size, including six novel genomes from Bartonella isolated from a cow, two moose, two dogs, and a kangaroo. A phylogenetic tree inferred from 428 orthologous core genes indicates that the deadly human pathogen B. bacilliformis is related to the ruminant-adapted clade, rather than being the earliest diverging species in the genus as previously thought. A gene flux analysis identified 12 genes for a GTA and a phage-derived origin of replication as the most conserved innovations. These are located in a region of a few hundred kb that also contains 8 insertions of gene clusters for type III, IV, and V secretion systems, and genes for putatively secreted molecules such as cholera-like toxins. The phylogenies indicate a recent transfer of seven genes in the virB gene cluster for a type IV secretion system from a catadapted B. henselae to a dog-adapted B. vinsonii strain. We show that the B. henselae GTA is functional and can transfer genes in vitro. We suggest that the maintenance of the GTA is driven by selection to increase the likelihood of horizontal gene transfer and argue that this process is beneficial at the population level, by facilitating adaptive evolution of the host-adaptation systems and thereby expansion of the host range size. The process counters gene loss and forces all cells to contribute to the production of the GTA and the secreted molecules. The results advance our understanding of the role that GTAs play for the evolution of bacterial genomes.
  •  
32.
  • Jafri, Yawer, et al. (författare)
  • A study of black liquor and pyrolysis oil co-gasification in pilot scale
  • 2018
  • Ingår i: Biomass Conversion and Biorefinery. - : Springer. - 2190-6815 .- 2190-6823. ; 8:1, s. 113-124
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of the blend ratio and reactor temperature on the gasification characteristics of pyrolysis oil (PO) and black liquor (BL) blends with up to 20 wt% PO was studied in a pilot-scale entrained-flow gasifier. In addition to unblended BL, three blends with PO/BL ratios of 10/90, 15/85, and 20/80 wt% were gasified at a constant load of 2.75 MWth. The 15/85 PO/BL blend was used to investigate the effect of temperature in the range 1000–1100 °C. The decrease in fuel inorganic content with increasing PO fraction resulted in more dilute green liquor (GL), and a greater portion of the feedstock carbon ended up in syngas as CO. As a consequence, the cold gas efficiency increased by about 5%-units. Carbon conversion was in the range 98.8–99.5% and did not vary systematically with either fuel composition or temperature. Although the measured reactor temperatures increased slightly with increasing PO fraction, both unblended BL and the 15% PO blend exhibited largely similar behavior in response to temperature variations. The results from this study show that blending BL with the more energy-rich PO can increase the cold gas efficiency and improve the process carbon distribution without adversely affecting either carbon conversion or the general process performance.
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33.
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34.
  • Karlsson Lindsjö, Oskar, et al. (författare)
  • The Effect of Preprocessing by Sequence-Independent, Single-Primer Amplification (SISPA) on Metagenomic Detection of Viruses
  • 2013
  • Ingår i: Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science. - : Mary Ann Liebert Inc. - 1538-7135 .- 1557-850X. ; 11, s. S227-S234
  • Tidskriftsartikel (refereegranskat)abstract
    • Compared to routine diagnostics, screening for pathogens in outbreak situations, with or without intentional release, poses demands on the detection technology to not only indicate the presence of already known causative agents but also novel and unexpected pathogens. The metagenomic approach to detecting viral pathogens, using unbiased high-throughput sequencing (HTS), is a well-established methodology with a broad detection range and wide applicability on different sample matrices. To prepare a sample for HTS, the common presequencing steps include homogenization, enrichment, separation (eg, magnetic separation), and amplification. In this initial study, we explored the benefits and drawbacks of preprocessing by sequence-independent, single-primer amplification (SISPA) of nucleic acids by applying the methodology to artificial samples. More specifically, a synthetic metagenome was divided into 2 samples, 1 unamplified and 1 diluted, and amplified by SISPA. Subsequently, both samples were sequenced using the Ion Torrent Personal Genome Machine (PGM), and the resulting datasets were analyzed by using bioinformatics, short read mapping, de novo assembly, BLAST-based taxonomic classification, and visualization. The results indicate that even though SISPA introduces a strong amplification bias, which makes it unsuitable for whole-genome sequencing, it is still useful for detecting and identifying viruses.
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35.
  • Karlsson Lindsjö, Oskar, et al. (författare)
  • Viral Metagenomics – New applications for the broad-range detection of viromes in veterinary and public health settings
  • 2013
  • Ingår i: EMBnet.journal. - 2226-6089. ; 19, s. 21-22
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Metagenomic methods for detection of viruses provide new diagnostic tools to the veterinary and public health laboratories, with powerful capacities to detect and to monitor the viromes in clinical samples. Our groups at the OIE Collaborating Centre for the Biotechnology-based Diagnosis of Infectious Diseases in Veterinary Medicine, Uppsala, Sweden and at the SLU Global Bioinformatics Centre, Uppsala, Sweden are working with the development and evaluation of the methodological and technological platforms for viral metagenomics. Together with the National Veterinary Institute (SVA), we develop and test methods for extraction of viromes, feasibility of sequencing platforms to deliver metagenomic data-sets and evaluate bioinformatics tools as well as combine them into software packages for analysis and exploration of metagenomes. The aim of the work is to provide insight into using the metagenomics approach for detection of emerging viruses.
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36.
  • Landälv, Ingvar, et al. (författare)
  • Two years experience of the BioDME project : A complete wood to wheel concept
  • 2014
  • Ingår i: Environmental Progress & Sustainable Energy. - : Wiley. - 1944-7442 .- 1944-7450. ; 33:3, s. 744-750
  • Tidskriftsartikel (refereegranskat)abstract
    • Dimethyl ether (DME), is an excellent diesel fuel that can be produced through gasification from multiple feedstocks. One particularly interesting renewable feedstock is the energy rich by-product from the pulping process called black liquor (BL). The concept of utilizing BL as gasifier feed, converting it via syngas to DME and then compensating the withdrawal of BL energy from the pulp mill by supplying biomass to a conventional combined heat and power plant, is estimated to be one of the most efficient conversion concepts of biomass to a renewable fuel on a well-to-wheel basis. This concept has been demonstrated by the four-year BioDME project, including field tests of DME-fueled heavy-duty trucks that are operated commercially. Up till the summer of 2013 more than 500 tons of BioDME has been produced and distributed to 10 HD trucks, which in total has run more than 1 million km in commercial service
  •  
37.
  • Lindberg, Siv M, et al. (författare)
  • Towards a cellulose-based society : Demonstrating the feasibility of new bio-based material concepts and products
  • 2016
  • Ingår i: Proceedings - D and E 2016: 10th International Conference on Design and Emotion - Celebration and Contemplation. - 9789461867254 ; , s. 411-419
  • Konferensbidrag (refereegranskat)abstract
    • In moving towards a cellulose-based society, interdisciplinary effort is required as it is at this interface that new ideas are found and can grow. New bio-based materials will play a key role but getting them into the marketplace is not always straightforward. Many options are available both for sourcing and for producing composite materials from wood-based cellulose and poly-lactic acid (PLA). Depending on how the material is processed, a multitude of properties can be generated. The main goal with this work was to attempt to reduce the research-To-market gap. This was done by testing a new way of working together where we bundled innovation-oriented projects and research-oriented projects around the theme of material experience. We then systematically worked with material demonstrators. In this article, we exemplify the results by focusing on one research-oriented project that did not at the outset have a market context and on one innovation-oriented project with clear market requirements. In addition to introducing a new concept in bundling research-oriented and innovation-oriented projects, this paper contributes several practical examples of what material demonstrators can do. We also present an application and analysis of Moultrie’s extended Science-Technology-Application-Market (STAM) model to analyze the material demonstrators and design phases of the bundled projects. We modified the proposed classification with different types of material demonstrators according to how close they are to an actual product segment. Designers and scientists worked together but with different emphasis in each phase.
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38.
  • Malmberg, Maja, et al. (författare)
  • Genetic characterization of a novel adenovirus detected in captive bottlenose dolphin (Tursiops truncates) suffering from self-limiting gastroenteritis
  • 2016
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Adenoviruses have a wide host range and are common pathogens in vertebrates. In cetaceans, adenoviruses have only rarely been detected and correlated with disease. A novel adenovirus was recently detected in captive bottlenose dolphin (Tursiops truncates) suffering from self-limiting gastroenteritis. The initial analysis of partial pol and hexon gene sequences indicated that this was a hitherto unknown adenovirus with less than 80% sequence identity to previously published sequences. The aim of this study was to further genetically characterize this novel adenovirus using a high-throughput sequencing approach for whole-genome sequencing. Fecal samples from affected bottlenose dolphins were collected as previously described. Samples were homogenized and centrifuged through filters with 0.22 μm pores. To remove non-viral DNA the filtrate was treated with DNase and RNase prior to DNA extraction. Nextera XT sequencing libraries were sequenced at the MiSeq platform. Sequence reads were assembled using the MIRA assembler. The longest contigs were used to identify the most similar reference genome using BLASTn. To generate a draft consensus sequence, matching contigs were aligned against the reference genome using CodonCode Aligner software. The complete genome sequence was verified using PCR and Sanger sequencing. The analysis of phylogenetic relationships was conducted in MEGA 5 [2]. Gene prediction and annotation were used using PROKKA, MAKER and GeneMark.hmm with heuristic models. High-throughput sequencing allowed the recovery of the complete sequence of Bottlenose dolphin Adenovirus-1 (BdAdV-1). The sequence is 34 040bp and has an ITR of about 220bp. A total of 26 coding sequences were identified out of which 3 were assigned as hypothetical and 23 were functionally annotated. The homology analysis indicates that the most similar genome is the Bottlenose dolphin Adenovirus 2 (KR024710) (71% identity), followed by the California sea lion adenovirus 1 (KJ563221), and then Bovine adenovirus type 2 (AF252854). We here describe the complete sequence of a recently identified adenovirus associated with gastroenteritis in dolphins. This virus is clearly different from previously published adenoviruses, demonstrating less than 72% sequence identity. A more in-depth analysis of the obtained sequence data and predicted proteins should allow predictions to be made regarding e.g. tropism. The study also demonstrate the usefulness of high-throughput sequencing to obtain full-length genomes of genetically divergent viruses.
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39.
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40.
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41.
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42.
  • Malmberg, Maja, et al. (författare)
  • Phylogenomic analysis of the complete sequence of a gastroenteritis-associated cetacean adenovirus (bottlenose dolphin adenovirus 1) reveals a high degree of genetic divergence
  • 2017
  • Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 53, s. 47-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Adenoviruses are common pathogens in vertebrates, infecting a wide range of hosts, but only having rarely been detected and correlated with disease in cetaceans. This article describes the first complete genomic sequence of a cetacean adenovirus, bottlenose dolphin adenovirus 1 (BdAdV-1), detected in captive bottlenose dolphin population ( Tursiops truncatus) suffering from self-limiting gastroenteritis. The complete genome sequence of BdAdV-1 was recovered from data generated by high-throughput sequencing and validated by Sanger sequencing. The genome is 34,080 bp long and has 220 nucleotides long inverted terminal repeats. A total of 29 coding sequences were identified, 26 of which were functionally annotated. Among the unusual features of this genome is a remarkably long 4380 bp E3 ORF1, that displays no sequence homology with the corresponding E3 regions of other adenoviruses. In addition, the fiber protein only has 26% identity with fiber proteins described in other adenoviruses. Three hypothetical proteins were predicted. The phylogenetic analysis indicates that the closest known relative to BdAdV-1 is an adenovirus detected in bottlenose dolphin (KR024710), with an amino acid sequence identity between 36 and 79% depending on the protein. Based on the phylogenic analysis, the BdAdV-1 appears to have co-evolved with its host.The results indicate that BdAdV-1 belongs to the Mastadenovirus genus of the Adenoviridae family, however, it is clearly different from other adenoviruses, especially in the 3'-end of the viral genome. The high degree of sequence divergence suggests that BdAdV-1 should be considered as a novel species in the Mastadenovirus genus. The study also demonstrates the usefulness of high-throughput sequencing to obtain full-length genomes of genetically divergent viruses. (C) 2017 The Authors. Published by Elsevier B.V.
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43.
  • Malmberg, Maja, et al. (författare)
  • The evolution of African swine fever virus in Sardinia (1978-2014) as revealed by whole-genome sequencing and comparative analysis
  • 2020
  • Ingår i: Transboundary and Emerging Diseases. - : Hindawi Limited. - 1865-1674 .- 1865-1682. ; 67, s. 1971-1980
  • Tidskriftsartikel (refereegranskat)abstract
    • African swine fever (ASF) is a highly contagious and lethal viral disease of pigs and wild boars, which is enzootic in many African countries and on the Italian island of Sardinia, where it has been present since 1978. Previous genetic analyses of Sardinian ASF virus (ASFV) isolates have revealed that they all belong to p72 genotype I, with only minor sequence variations. However, these studies examined only a few selected genes. To distinguish between these closely related isolates and better investigate ASFV evolution in Sardinia, we sequenced the complete genomes of 12 Sardinian ASFV isolates collected between 1978 and 2012, and compared them with 47/Ss/2008 and 26544/OG10. Most of the observed changes occurred in a time-dependent manner; however, their biological significance remains unclear. As a whole, our results demonstrate the remarkable genetic stability of these strains, supporting a single-source introduction of the virus.
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44.
  • Norkko, Joanna, et al. (författare)
  • Ecosystem functioning along gradients of increasing hypoxia and changing soft-sediment community types
  • 2019
  • Ingår i: Journal of Sea Research. - : Elsevier BV. - 1385-1101 .- 1873-1414. ; 153
  • Tidskriftsartikel (refereegranskat)abstract
    • Marine ecosystems world-wide are threatened by oxygen deficiency, with potential serious consequences for ecosystem functioning and the goods and services they provide. While the effects of hypoxia on benthic species diversity are well documented, the effects on ecosystem function have only rarely been assessed in real-world settings. To better understand the links between structural changes in macro- and meiofaunal communities, hypoxic stress and benthic ecosystem function (benthic nutrient fluxes, community metabolism), we sampled a total of 11 sites in Havstensfjord and Askeröfjord (Swedish west coast) in late summer, coinciding with the largest extent and severity of seasonal hypoxia in the area. The sites spanned oxic to anoxic bottom water, and a corresponding gradient in faunal diversity. Intact sediment cores were incubated to measure fluxes of oxygen and nutrients (NO3−, NO2−, NH4+, PO43−, SiO4) across the sediment-water interface. Sediment profile imaging (SPI) footage was obtained from all sites to assess structural elements and the bioturbation depth, and additional samples were collected to characterise sediment properties and macro- and meiofaunal community composition. Bottom-water O2 concentration was the main driver of macrofauna communities, with highest abundance and biomass, as well as variability, at the sites with intermediate O2 concentration. Meiofauna on the other hand was less sensitive to bottom-water O2 concentration. Oxygen was the main driver of nutrient fluxes too, but macrofauna as well meiofauna were also significant predictors; DistLM analyses indicated that O2 concentration, macrofaunal abundance or biomass, and meiofaunal abundance collectively explained 63%, 30% and 28% of the variation in sediment O2 consumption, NH4+flux and PO43− flux, respectively. The study provides a step towards a more realistic understanding of the link between benthic fauna and ecosystem functioning, and the influence of disturbance on this relationship, which is important for management decisions aimed at protecting the dwindling biodiversity in the coastal zones around the world.
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45.
  • Nystedt, Björn, 1978-, et al. (författare)
  • Evolution of Host Adaptation Systems in  the Mammalian Blood Specialist Bartonella
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Bacteria of the genus Bartonella are facultative intracellular bacteria infecting the red blood cells of mammals. Bartonella isolates have now been reported from a wide range of mammalian host species, including humans, domestic animals such as pets and livestock, as well as many wild animals such as deer, moose, kangaroo, and whales. Here, we present the first major genus-wide investigation of host-adaptation systems in Bartonella, using 5 published and 5 draft genome sequences. The sampling includes both clinical and natural isolates, and represent well the major phylogenetic diversity of the genus. Our study reveals four distinct protein families of Type V Secretion Systems (T5SS) shared by all sequenced members of the genus. We also show that a recently identified gene transfer agent (GTA) consisting of a defective phage is, surprisingly, the most conserved gene cluster among all Bartonella-specific or imported genes, strongly emphasizing the functional importance of this system for the life-style and evolution of Bartonella.
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46.
  • Plattén, Michael, et al. (författare)
  • Deep Learning Corpus Callosum Segmentation as a Neurodegenerative Marker in Multiple Sclerosis.
  • 2021
  • Ingår i: Journal of Neuroimaging. - : Wiley. - 1051-2284 .- 1552-6569. ; 31:3, s. 493-500
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Corpus callosum atrophy is a sensitive biomarker of multiple sclerosis (MS) neurodegeneration but typically requires manual 2D or volumetric 3D-based segmentations. We developed a supervised machine learning algorithm, DeepnCCA, for corpus callosum segmentation and relate callosal morphology to clinical disability using conventional MRI scans collected in clinical routine.METHODS: In a prospective study of 553 MS patients with 704 acquisitions, 200 unique 2D T2 -weighted MRI scans were delineated to develop, train, and validate DeepnCCA. Comparative FreeSurfer segmentations were obtained in 504 3D T1 -weighted scans. Both FreeSurfer and DeepnCCA outputs were correlated with clinical disability. Using principal component analysis of the DeepnCCA output, the morphological changes were explored in relation to clinical disease burden.RESULTS: .76%, for intracranial and corpus callosum area, respectively through 10-fold cross-validation). DeepnCCA had numerically stronger correlations with cognitive and physical disability as compared to FreeSurfer: Expanded disability status scale (EDSS) ±6 months (r = -.22 P = .002; r = -.17, P = .013), future EDSS (r = -.26, P<.001; r = -.17, P = .012), and future symbol digit modalities test (r = .26, P = .001; r = .24, P = .003). The corpus callosum became thinner with increasing cognitive and physical disability. Increasing physical disability, additionally, significantly correlated with a more angled corpus callosum.CONCLUSIONS: DeepnCCA (https://github.com/plattenmichael/DeepnCCA/) is an openly available tool that can provide fast and accurate corpus callosum measurements applicable to large MS cohorts, potentially suitable for monitoring disease progression and therapy response.
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47.
  • Platten, Michael (författare)
  • Quantitative MRI Biomarkers of Neurodegeneration in Multiple Sclerosis
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that targets myelin in the brain and spinal cord. The corpus callosum connects the cerebral hemispheres and is composed of heavily myelinated axons. Atrophy of the corpus callosum has been explored as a more sensitive marker of disease status and neurodegeneration relative to other neuroanatomical structures. However, development of more accurate, precise and less labor demanding tools for characterizing callosal atrophy would increase its potential as a proxy marker of MS evolution.Purpose: The primary objective of this thesis was to evaluate and develop quantitative methods for measuring neurodegeneration in MS with a focus on the corpus callosum. This was achieved through the comparison of the accuracy and precision of manual delineation, conventional volumetric methods, and machine learning approaches.Study I: In a prospective study, 9 MS patients underwent scan/re-scanning with and without repositioning to measure the precision and accuracy of manual versus volumetric cross-sectional and longitudinal FreeSurfer analyses. While the longitudinal stream of FreeSurfer revealed the highest precision, the overall limitations on accuracy warrants caution.Study II: In a prospective study, 553 MS patients with 704 2D T2-weighted MRI acquisitions were used to train and validate a machine learning algorithm for segmenting a marker of neurodegeneration. The algorithm quickly produced highly accurate segmentations of the corpus callosum and brain (Dice Coefficient: 89% and 98%, respectively). The algorithm had numerically higher correlations to neurologic disability as compared to FreeSurfer.Study III: Analogous to Study II, in a prospective study, 631 MS patients with 3D T1-weighted and T2-weighted FLAIR acquisitions were used to train and validate a machine learning algorithm for segmenting the mid-sagittal normalized corpus callosum area. The algorithm performed better with T1-weighted scans and less atrophied patients. Scanner parameters had no significant effect on the T1-weighted output. The algorithm produced segmentations in less than a minute per scan, with similar correlations to neurologic disability, as compared to FreeSurfer.Study IV: In a prospective study, 92 MS patients acquired both 3 and 7 Tesla brain MRI scans to reveal the lobe-specific lesion volumes’ association to corpus callosum atrophy, where lesion burden was found to be greatest in the frontal and parietal lobes. In addition, the posterior portions of the corpus callosum provided the strongest fit linear regression models, with a combination of white matter lesions and intracortical lesions predicting atrophy.Conclusions: Creating and evaluating novel tools for measuring neurodegeneration over time is important both for monitoring disease progression and to evaluate therapeutic responses with current drugs. As novel therapeutic strategies appear, it may also help in assessing neuroregenerative approaches.
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48.
  • Rodrigues De Miranda, Joachim, et al. (författare)
  • Cold case : The disappearance of Egypt bee virus, a fourth distinct master strain of deformed wing virus linked to honeybee mortality in 1970's Egypt
  • 2022
  • Ingår i: Virology Journal. - : BioMed Central (BMC). - 1743-422X. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • In 1977, a sample of diseased adult honeybees (Apis mellifera) from Egypt was found to contain large amounts of a previously unknown virus, Egypt bee virus, which was subsequently shown to be serologically related to deformed wing virus (DWV). By sequencing the original isolate, we demonstrate that Egypt bee virus is in fact a fourth unique, major variant of DWV (DWV-D): more closely related to DWV-C than to either DWV-A or DWV-B. DWV-A and DWV-B are the most common DWV variants worldwide due to their close relationship and transmission by Varroa destructor. However, we could not find any trace of DWV-D in several hundred RNA sequencing libraries from a worldwide selection of honeybee, varroa and bumblebee samples. This means that DWV-D has either become extinct, been replaced by other DWV variants better adapted to varroa-mediated transmission, or persists only in a narrow geographic or host range, isolated from common bee and beekeeping trade routes.
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49.
  • Rodrigues De Miranda, Joachim, et al. (författare)
  • Virus Diversity and Loads in Crickets Reared for Feed: Implications for Husbandry
  • 2021
  • Ingår i: Frontiers in Veterinary Science. - : Frontiers Media SA. - 2297-1769. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Insects generally have high reproductive rates leading to rapid population growth and high local densities; ideal conditions for disease epidemics. The parasites and diseases that naturally regulate wild insect populations can also impact when these insects are produced commercially, on farms. While insects produced for human or animal consumption are often reared under high density conditions, very little is known about the microbes associated with these insects, particularly those with pathogenic potential. In this study we used both target-free and targeted screening approaches to explore the virome of two cricket species commonly reared for feed and food, Acheta domesticus and Gryllus bimaculatus. The target-free screening of DNA and RNA from a single A. domesticus frass sample revealed that only 1% of the nucleic acid reads belonged to viruses, including known cricket, insect, bacterial and plant pathogens, as well as a diverse selection of novel viruses. The targeted screening revealed relatively high levels of Acheta domesticus densovirus, invertebrate iridovirus 6 and a novel iflavirus, as well as low levels of Acheta domesticus volvovirus, in insect and frass samples from several retailers. Our findings highlight the value of multiple screening approaches for a comprehensive and robust cricket disease monitoring and management strategy. This will become particularly relevant as-and-when cricket rearing facilities scale up and transform from producing insects for animal feed to producing insects for human consumption.
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50.
  • Rodrigues De Miranda, Joachim, et al. (författare)
  • Virus Prospecting in Crickets-Discovery and Strain Divergence of a Novel Iflavirus in Wild and Cultivated Acheta domesticus
  • 2021
  • Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Orthopteran insects have high reproductive rates leading to boom-bust population dynamics with high local densities that are ideal for short, episodic disease epidemics. Viruses are particularly well suited for such host population dynamics, due to their supreme ability to adapt to changing transmission criteria. However, very little is known about the viruses of Orthopteran insects. Since Orthopterans are increasingly reared commercially, for animal feed and human consumption, there is a risk that viruses naturally associated with these insects can adapt to commercial rearing conditions, and cause disease. We therefore explored the virome of the house cricket Acheta domesticus, which is both part of the natural Swedish landscape and reared commercially for the pet feed market. Only 1% of the faecal RNA and DNA from wild-caught A. domesticus consisted of viruses. These included both known and novel viruses associated with crickets/insects, their bacterial-fungal microbiome, or their plant food. Relatively abundant among these viral Operational Taxonomic Units (OTUs) was a novel Iflavirus, tentatively named Acheta domesticus Iflavirus (AdIV). Quantitative analyses showed that AdIV was also abundant in frass and insect samples from commercially reared crickets. Interestingly, the wild and commercial AdIV strains had short, extremely divergent variation hotspots throughout the genome, which may indicate specific adaptation to their hosts' distinct rearing environments.
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