| 1. |
- Bengtsson-Palme, Johan, 1985, et al.
(författare)
-
The human gut microbiome as a transporter of antibiotic resistance genes between continents
- 2015
-
Ingår i: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 59:10, s. 6551-6560
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.
|
|
| 2. |
- Brownstein, Catherine A., et al.
(författare)
-
An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
-
Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
|
|
| 3. |
- Danielsson, Frida, et al.
(författare)
-
Transcriptome profiling of the interconnection of pathways involved in malignant transformation and response to hypoxia
- 2018
-
Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 9:28, s. 19730-19744
-
Tidskriftsartikel (refereegranskat)abstract
- In tumor tissues, hypoxia is a commonly observed feature resulting from rapidly proliferating cancer cells outgrowing their surrounding vasculature network. Transformed cancer cells are known to exhibit phenotypic alterations, enabling continuous proliferation despite a limited oxygen supply. The four-step isogenic BJ cell model enables studies of defined steps of tumorigenesis: the normal, immortalized, transformed, and metastasizing stages. By transcriptome profiling under atmospheric and moderate hypoxic (3% O2) conditions, we observed that despite being highly similar, the four cell lines of the BJ model responded strikingly different to hypoxia. Besides corroborating many of the known responses to hypoxia, we demonstrate that the transcriptome adaptation to moderate hypoxia resembles the process of malignant transformation. The transformed cells displayed a distinct capability of metabolic switching, reflected in reversed gene expression patterns for several genes involved in oxidative phosphorylation and glycolytic pathways. By profiling the stage-specific responses to hypoxia, we identified ASS1 as a potential prognostic marker in hypoxic tumors. This study demonstrates the usefulness of the BJ cell model for highlighting the interconnection of pathways involved in malignant transformation and hypoxic response.
|
|
| 4. |
- Eggert, Erik, et al.
(författare)
-
Medical and biological factors affecting mortality in elderly residential fire victims : a narrative review of the literature
- 2017
-
Ingår i: Scars, Burns & Healing. - : SAGE Publications. - 2059-5131. ; 3
-
Tidskriftsartikel (refereegranskat)abstract
- For older people (aged over 65 years), the risk of dying in a residential fire is doubled compared to the general population. Obvious causes of death mainly include smoke inhalation and burn injuries. That older people are more fragile and have more concurrent diseases is inherent, but what is it that makes them more vulnerable? It is known that the number of elderly people is increasing globally and that the increased risk of death in fires can be explained, at least in part, by physical and/or cognitive disabilities as well as socioeconomic and behavioural factors. The possibility that medical illnesses and an aging organism/tissues might explain this increased risk has not been shown to the same extent. Therefore, this narrative literature review focuses on medical and biological explanations. An initial search using the terms ‘elderly’, ‘fatal’, ‘residential’ and ‘fire’ yielded some interesting articles. Using a broader snowball search also accepting grey literature, several additional risk factors could be identified. Cardiovascular diseases, in particular atherosclerotic heart disease, greatly increases the vulnerability to, for example, carbon monoxide and probably also other asphyxiating gases. Cardiovascular diseases and lack of physical fitness may also increase vulnerability to heat. Burned elderly patients are also at a higher risk of death than younger patients, but it is controversial whether it is age itself or the pre-existing illnesses that come with age that increase the risk. Immunosenescence, malnutrition and female gender are other risk factors for poorer outcome after burns, all of which are common among older people.
|
|
| 5. |
- Ekström, Andreas, 1979, et al.
(författare)
-
Cardiorespiratory adjustments to chronic environmental warming improve hypoxia tolerance in European perch (Perca fluviatilis).
- 2021
-
Ingår i: The Journal of experimental biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 224:6
-
Tidskriftsartikel (refereegranskat)abstract
- Aquatic hypoxia will become increasingly prevalent in the future as a result of eutrophication combined with climate warming. While short-term warming typically constrains fish hypoxia tolerance, many fishes cope with warming by adjusting physiological traits through thermal acclimation. Yet, little is known about how such adjustments affect tolerance to hypoxia. We examined European perch (Perca fluviatilis) from the Biotest enclosure (23°C, Biotest population), a unique ∼1km2 ecosystem artificially warmed by cooling water from a nuclear power plant, and an adjacent reference site (16-18°C, reference population). Specifically, we evaluated how acute and chronic warming affect routine oxygen consumption rate (ṀO2,routine) and cardiovascular performance in acute hypoxia, alongside assessment of the thermal acclimation of the aerobic contribution to hypoxia tolerance (critical O2 tension for ṀO2,routine: Pcrit) and absolute hypoxia tolerance (O2 tension at loss of equilibrium; PLOE). Chronic adjustments (possibly across lifetime or generations) alleviated energetic costs of warming in Biotest perch by depressing ṀO2,routine and cardiac output, and by increasing blood O2 carrying capacity relative to reference perch acutely warmed to 23°C. These adjustments were associated with improved maintenance of cardiovascular function and ṀO2,routine in hypoxia (i.e. reduced Pcrit). However, while Pcrit was only partially thermally compensated in Biotest perch, they had superior absolute hypoxia tolerance (i.e. lowest PLOE) relative to reference perch irrespective of temperature. We show that European perch can thermally adjust physiological traits to safeguard and even improve hypoxia tolerance during chronic environmental warming. This points to cautious optimism that eurythermal fish species may be resilient to the imposition of impaired hypoxia tolerance with climate warming.
|
|
| 6. |
- Farinotti, Daniel, et al.
(författare)
-
Results from the Ice Thickness Models Intercomparison eXperiment Phase 2 (ITMIX2)
- 2021
-
Ingår i: Frontiers in Earth Science. - : Frontiers Media S.A.. - 2296-6463. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- Knowing the ice thickness distribution of a glacier is of fundamental importance for a number of applications, ranging from the planning of glaciological fieldwork to the assessments of future sea-level change. Across spatial scales, however, this knowledge is limited by the paucity and discrete character of available thickness observations. To obtain a spatially coherent distribution of the glacier ice thickness, interpolation or numerical models have to be used. Whilst the first phase of the Ice Thickness Models Intercomparison eXperiment (ITMIX) focused on approaches that estimate such spatial information from characteristics of the glacier surface alone, ITMIX2 sought insights for the capability of the models to extract information from a limited number of thickness observations. The analyses were designed around 23 test cases comprising both real-world and synthetic glaciers, with each test case comprising a set of 16 different experiments mimicking possible scenarios of data availability. A total of 13 models participated in the experiments. The results show that the inter-model variability in the calculated local thickness is high, and that for unmeasured locations, deviations of 16% of the mean glacier thickness are typical (median estimate, three-quarters of the deviations within 37% of the mean glacier thickness). This notwithstanding, limited sets of ice thickness observations are shown to be effective in constraining the mean glacier thickness, demonstrating the value of even partial surveys. Whilst the results are only weakly affected by the spatial distribution of the observations, surveys that preferentially sample the lowest glacier elevations are found to cause a systematic underestimation of the thickness in several models. Conversely, a preferential sampling of the thickest glacier parts proves effective in reducing the deviations. The response to the availability of ice thickness observations is characteristic to each approach and varies across models. On average across models, the deviation between modeled and observed thickness increase by 8.5% of the mean ice thickness every time the distance to the closest observation increases by a factor of 10. No single best model emerges from the analyses, confirming the added value of using model ensembles.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Johansson, Henrik J., et al.
(författare)
-
Breast cancer quantitative proteome and proteogenomic landscape
- 2019
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.
|
|
| 13. |
- Lindskog, Cecilia, et al.
(författare)
-
The human cardiac and skeletal muscle proteomes defined by transcriptomics and antibody-based profiling
- 2015
-
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 16
-
Tidskriftsartikel (refereegranskat)abstract
- Background: To understand cardiac and skeletal muscle function, it is important to define and explore their molecular constituents and also to identify similarities and differences in the gene expression in these two different striated muscle tissues. Here, we have investigated the genes and proteins with elevated expression in cardiac and skeletal muscle in relation to all other major human tissues and organs using a global transcriptomics analysis complemented with antibody-based profiling to localize the corresponding proteins on a single cell level. Results: Our study identified a comprehensive list of genes expressed in cardiac and skeletal muscle. The genes with elevated expression were further stratified according to their global expression pattern across the human body as well as their precise localization in the muscle tissues. The functions of the proteins encoded by the elevated genes are well in line with the physiological functions of cardiac and skeletal muscle, such as contraction, ion transport, regulation of membrane potential and actomyosin structure organization. A large fraction of the transcripts in both cardiac and skeletal muscle correspond to mitochondrial proteins involved in energy metabolism, which demonstrates the extreme specialization of these muscle tissues to provide energy for contraction. Conclusions: Our results provide a comprehensive list of genes and proteins elevated in striated muscles. A number of proteins not previously characterized in cardiac and skeletal muscle were identified and localized to specific cellular subcompartments. These proteins represent an interesting starting point for further functional analysis of their role in muscle biology and disease.
|
|
| 14. |
- Ovegård, Erik, et al.
(författare)
-
Operational Guidance with Respect to Pure Loss of Stability and Parametric Rolling
- 2012
-
Ingår i: Proceedings of the 11<sup>th</sup> International Conference on the Stability of Ships and Ocean Vehicles (STAB2012).
-
Konferensbidrag (refereegranskat)abstract
- This paper reviews two previously presented simplified methods for assessment of pure loss of stability and parametric rolling based on linear signal theory. The methods are evaluated in relation to full-scale incidents and time-domain simulations. Underlying assumptions and tuning of the critical levels in the simplified methods with reference to time-domain simulations is discussed. Given proper tuning the methods are concluded to provide a feasible basis for ship specific on-board operational guidance.
|
|
| 15. |
- Rein-Hedin, Erik, et al.
(författare)
-
First-in-Human Study to Assess the Safety, Tolerability, and Pharmacokinetics of Pirepemat, a Cortical Enhancer, in Healthy Volunteers
- 2021
-
Ingår i: Clinical Pharmacology in Drug Development. - : John Wiley & Sons. - 2160-763X .- 2160-7648. ; 10:12, s. 1485-1494
-
Tidskriftsartikel (refereegranskat)abstract
- Pirepemat (IRL752) is a cortical enhancer being developed for the prevention of falls in patients with Parkinson disease. This first-in-human, randomized, double-blind, placebo-controlled phase 1 study evaluated safety, tolerability, and pharmacokinetics (PK) of pirepemat administered as oral single ascending doses (10, 35, 75, 175, 350 mg) and multiple ascending doses (100 and 250 mg 3 times daily) for 7 days to healthy male volunteers. Twenty and 24 subjects were randomly assigned in the single ascending dose and multiple ascending doses parts of the study, respectively. Pirepemat was generally well tolerated, although an increased frequency of adverse events of mild intensity within nervous system disorders (headache and dizziness) was seen after administration of 350 mg as a single dose and after multiple doses of 100 and 250 mg. PK of pirepemat showed a linear relationship over the dose range studied and exhibited dose proportionality after multiple-dose administration. Accumulation after 7 days of multiple dosing was minor. Absorption was rapid, with a median time to maximum concentration of 2.0 hours on day 1 and day 7 (100 and 250 mg) and a mean terminal half-life between 3.7 and 5.2 hours. Food intake had no (obvious) impact on PK. The results support 3-times-daily dosing and further clinical development.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Söder, Carl-Johan, et al.
(författare)
-
Parametric roll mitigation using rudder control
- 2013
-
Ingår i: Journal of Marine Science and Technology. - : Springer Science and Business Media LLC. - 0948-4280 .- 1437-8213. ; 18:3, s. 395-403
-
Tidskriftsartikel (refereegranskat)abstract
- Severe roll angles can be developed by parametric excitation in relatively moderate weather without any apparent pre-warning for the crew onboard. In this study the prospect of using rudder control to mitigate parametric roll was investigated using multi-degree of freedom simulations. A typical modern Pure Car and Truck Carrier was considered and modelled by coupling a roll model with a planar motion manoeuvring model. The combined model was calibrated using in-service, full-scale trials and model tests. Irregular variations of the metacentric height were applied to simulate recorded, full-scale events of parametric roll that have occurred with the considered design. These simulations with rudder roll control showed promising results and demonstrate that the approach could be very efficient for mitigation of parametric roll.
|
|
