| 1. |
- Barrientos-Somarribas, Mauricio, et al.
(författare)
-
Discovering viral genomes in human metagenomic data by predicting unknown protein families
- 2018
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Massive amounts of metagenomics data are currently being produced, and in all such projects a sizeable fraction of the resulting data shows no or little homology to known sequences. It is likely that this fraction contains novel viruses, but identification is challenging since they frequently lack homology to known viruses. To overcome this problem, we developed a strategy to detect ORFan protein families in shotgun metagenomics data, using similarity-based clustering and a set of filters to extract bona fide protein families. We applied this method to 17 virus-enriched libraries originating from human nasopharyngeal aspirates, serum, feces, and cerebrospinal fluid samples. This resulted in 32 predicted putative novel gene families. Some families showed detectable homology to sequences in metagenomics datasets and protein databases after reannotation. Notably, one predicted family matches an ORF from the highly variable Torque Teno virus (TTV). Furthermore, follow-up from a predicted ORFan resulted in the complete reconstruction of a novel circular genome. Its organisation suggests that it most likely corresponds to a novel bacteriophage in the microviridae family, hence it was named bacteriophage HFM.
|
|
| 2. |
- Karlsson, Elin, et al.
(författare)
-
Revealing Different Roles of the mTOR-Targets S6K1 and S6K2 in Breast Cancer by Expression Profiling and Structural Analysis
- 2015
-
Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 10:12, s. e0145013-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe AKT/mTORC1/S6K pathway is frequently overstimulated in breast cancer, constituting a promising therapeutic target. The benefit from mTOR inhibitors varies, likely as a consequence of tumour heterogeneity, and upregulation of several compensatory feed-back mechanisms. The mTORC1 downstream effectors S6K1, S6K2, and 4EBP1 are amplified and overexpressed in breast cancer, associated with a poor outcome and divergent endocrine treatment benefit. S6K1 and S6K2 share high sequence homology, but evidence of partly distinct biological functions is emerging. The aim of this work was to explore possible different roles and treatment target potentials of S6K1 and S6K2 in breast cancer.Materials and methodsWhole-genome expression profiles were compared for breast tumours expressing high levels of S6K1, S6K2 or 4EBP1, using public datasets, as well as after in vitro siRNA downregulation of S6K1 and/or S6K2 in ZR751 breast cancer cells. In silico homology modelling of the S6K2 kinase domain was used to evaluate its possible structural divergences to S6K1.ResultsGenome expression profiles were highly different in S6K1 and S6K2 high tumours, whereas S6K2 and 4EBP1 profiles showed significant overlaps, both correlated to genes involved in cell cycle progression, among these the master regulator E2F1. S6K2 and 4EBP1 were inversely associated with IGF1 levels, and their prognostic value was shown to be restricted to tumours positive for IGFR and/or HER2. In vitro, S6K1 and S6K2 silencing resulted in upregulation of genes in the mTORC1 and mTORC2 complexes. Isoform-specific silencing also showed distinct patterns, e.g. S6K2 downregulation lead to upregulation of several cell cycle associated genes. Structural analyses of the S6K2 kinase domain showed unique structure patterns, deviating from those of S6K1, facilitating the development of isoform-specific inhibitors. Our data support emerging proposals of distinct biological features of S6K1 and S6K2, suggesting their importance as separate oncogenes and clinical markers, where specific targeting in different breast cancer subtypes could facilitate further individualised therapies.
|
|
| 3. |
- Röding, Fredrik, et al.
(författare)
-
Epidemiologic patterns of injuries treated at the emergency department of a Swedish medical center
- 2015
-
Ingår i: Injury Epidemiology. - : Springer. - 2197-1714. ; 2:3, s. ?-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The injury spectrum published in the literature has mainly been presented for a certain age group, as elderly or for a certain type of injury, as fracture and often restricted to in-hospital care cases. Our objective was to give an overview of the major types of injuries for all age groups and trends in the adult population.Methods: We analyzed 68,159 adult injury events, which occurred between 1999 and 2008 and was treated at the Emergency Department of Umea University Hospital. All these injuries are registered in a database. The injuries were analyzed depending on frequency, type of injury, and activity at the time of injury. Incidence rates were calculated using population data from Statistics Sweden.Results: Injury event incidence varied between 614 (2004) and 669 (2007) per 10,000 persons. The most common injury was a fracture, although contusions and wounds were also frequent. Fractures were responsible for almost three quarters of hospital days related to injury. The risk for fractures increased with age, as did contusions and concussions, whereas sprains decreased with age. Fracture incidence increased among the 50- to 59-year age group for both women and men. Fall-related injuries increased significantly for middle-aged adults. Sports-related and work injuries decreased, while injuries occurring during leisure time increased the most.Conclusion: A fracture is the most frequent type of injury for adults and accounts for the largest proportion of the trauma care burden. Contusions are also common and responsible for a significant proportion of the in-hospital days. Injuries caused by a fall increased among middle-age adults imply a need for an extension of fall prevention programs.
|
|
| 4. |
- Röding, Fredrik, et al.
(författare)
-
Trauma recidivism at an emergency department of a Swedish medical center
- 2016
-
Ingår i: Injury Epidemiology. - : Springer Science and Business Media LLC. - 2197-1714. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To inform targeted prevention, we studied patterns of trauma recidivism and whether a first injury predicts the risk for a recurrent injury.METHODS: In a population-based study of 98,502 adult injury events 1999-2012, at the emergency department of Umeå University Hospital, Sweden, we compared non-recidivists with recidivists in terms of patients' sex, age, type of injury and severity of the injury.RESULTS: Thirty-six percent of all patients suffered recurrent injuries, which were associated with a higher proportion of inpatient care and more hospital days. Young men and elderly women were at the highest risk for trauma recidivism. At 20 to 24 years, men had a 2.4 (CI 95 % 2.3-2.5) higher risk than women, a 90 years old woman had almost a 10-fold higher risk for another moderate/severe injury than a 20 years old one. A fracture were associated with a hazard ratio of 1.28 (CI 95 % 1.15-1.42) among men younger than 65 years and 1.31 (CI 95 % 1.12-1.54) for men older than 65 years for a subsequent moderate/severe injury. For women younger than 65 years a fracture was associated with a hazard ratio of 1.44 (CI 95 % 1.28-1.62) for a subsequent moderate/severe injury. A sprain carries a higher risk for a new moderate/severe injury for both men and women and in both age groups; the hazard ratio was 1.13 (CI 95 % 1.00-1.26) for men younger than 65 years, 1.42 (CI 95 % 1.01-1.99) for men older than 65 years, 1.19 (CI 95 % 1.05-1.35) for women younger than 65 years and 1.26 (CI 95 % 1.02-1.56) for women older than 65 years. A higher degree of injury severity was associated with a higher risk for a new moderate/severe injury.CONCLUSION: Trauma recidivism is common and represents a large proportion of all injured. Age and sex are associated with the risk for new injury. Injury types and severity, also have implications for future injury.
|
|
