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| 2. |
- Santangelo, James S., et al.
(författare)
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Global urban environmental change drives adaptation in white clover
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375
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Tidskriftsartikel (refereegranskat)abstract
- Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural dines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale.
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| 3. |
- Iacopetta, B, et al.
(författare)
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Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.
- 2006
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Ingår i: Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. - : Elsevier BV. - 0923-7534. ; 17:5, s. 842-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.
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| 6. |
- Ullemar, V., et al.
(författare)
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Heritability and confirmation of genetic association studies for childhood asthma in twins
- 2016
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Ingår i: Allergy. - Stockholm : Wiley. - 0105-4538 .- 1398-9995. ; 71:2, s. 230-238
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlthough the genetics of asthma has been extensively studied using both quantitative and molecular genetic analysis methods, both approaches lack studies specific to the childhood phenotype and including other allergic diseases. This study aimed to give specific estimates for the heritability of childhood asthma and other allergic diseases, to attempt to replicate findings from genomewide association studies (GWAS) for childhood asthma and to test the same variants against other allergic diseases. MethodsIn a cohort of 25 306 Swedish twins aged 9 or 12 years, data on asthma were available from parental interviews and population-based registers. The interviews also inquired about wheeze, hay fever, eczema, and food allergy. Through structural equation modeling, the heritability of all phenotypes was calculated. A subset of 10 075 twins was genotyped for 16 single nucleotide polymorphisms (SNPs) selected from previous GWAS; these were first tested for association with asthma and significant findings also against the other allergic diseases. ResultsThe heritability of any childhood asthma was 0.82 (95% CI 0.79-0.85). For the other allergic diseases, the range was approximately 0.60-0.80. Associations for six SNPs with asthma were replicated, including rs2305480 in the GSDMB gene (OR 0.80, 95% CI 0.74-0.86, P = 1.5*10(-8); other significant associations all below P = 3.5*10(-4)). Of these, only rs3771180 in IL1RL1 was associated with any other allergic disease (for hay fever, OR 0.64, 95% CI 0.53-0.77, P = 2.5*10(-6)). ConclusionAsthma and allergic diseases of childhood are highly heritable, and these high-risk genetic variants associated specifically with childhood asthma, except for one SNP shared with hay fever.
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| 9. |
- Viktorin, Alexander, et al.
(författare)
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The risk of switch to mania in patients with bipolar disorder during treatment with antidepressants alone and in combination with a mood stabilizer
- 2014
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Ingår i: The American Journal of Psychiatry. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0002-9556 .- 0002-953X .- 1535-7228.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study examined the risk of antidepressant-induced manic switch in patients with bipolar disorder treated either with antidepressant monotherapy or with an antidepressant in conjunction with a mood stabilizer. Method: Using Swedish national registries, the authors identified 3,240 patients with bipolar disorder who started treatment with an antidepressant and had no antidepressant treatment during the previous year. Patients were categorized into those receiving antidepressant monotherapy and those receiving an antidepressant plus a mood stabilizer. A within-individual design was used to control for confounding by disorder severity, genetic makeup, and early environmental factors. Cox regression analyses conditioned on individual were used to compare the rate of mania 0–3 months and 3–9 months after the start of antidepressant treatment with a preceding non-treatment period. Results: Nearly 35% of the patients were treated with antidepressant monotherapy. The increased risk of treatment-emergent mania was confined to patients on antidepressant monotherapy (hazard ratio=2.83, 95% CI=1.12, 7.19). Among patients treated with a concurrent mood stabilizer, no acute change in risk of mania was observed during the 3 months after the start of antidepressant treatment (hazard ratio=0.79, 95% CI=0.54, 1.15), and a decreased risk was observed during the period 3–9 months after treatment initiation (hazard ratio=0.63, 95% CI=0.42, 0.93). Conclusions: In this national registry study, antidepressant monotherapy was associated with an increased risk of mania. However, no risk of mania was seen in patients receiving an antidepressant while treated with a mood stabilizer. The results highlight the importance of avoiding antidepressant monotherapy in the treatment of bipolar disorder.
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| 10. |
- Viktorin, Alexander, et al.
(författare)
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The Risk of Treatment-Emergent Mania With Methylphenidate in Bipolar Disorder
- 2017
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Ingår i: American Journal of Psychiatry. - Arlington, USA : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 174:4, s. 341-348
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The authors sought to determine the risk of treatment-emergent mania associated with methylphenidate, used in monotherapy or with a concomitant mood-stabilizing medication, in patients with bipolar disorder.Method: Using linked Swedish national registries, the authors identified 2,307 adults with bipolar disorder who initiated therapy with methylphenidate between 2006 and 2014. The cohort was divided into two groups: those with and those without concomitant mood-stabilizing treatment. To adjust for individual-specific confounders, including disorder severity, genetic makeup, and early environmental factors, Cox regression analyses were used, conditioning on individual to compare the rate of mania (defined as hospitalization for mania or a new dispensation of stabilizing medication) 0-3 months and 3-6 months after medication start following nontreated periods.Results: Patients on methylphenidate monotherapy displayed an increased rate of manic episodes within 3 months of medication initiation (hazard ratio=6.7, 95% CI=2.0-22.4), with similar results for the subsequent 3 months. By contrast, for patients taking mood stabilizers, the risk of mania was lower after starting methylphenidate (hazard ratio=0.6, 95% CI=0.4-0.9). Comparable results were observed when only hospitalizations for mania were counted.Conclusions: No evidence was found for a positive association between methylphenidate and treatment-emergent mania among patients with bipolar disorder who were concomitantly receiving a mood-stabilizing medication. This is clinically important given that up to 20% of people with bipolar disorder suffer from comorbid ADHD. Given the markedly increased hazard ratio of mania following methylphenidate initiation in bipolar patients not taking mood stabilizers, careful assessment to rule out bipolar disorder is indicated before initiating monotherapy with psychostimulants.
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| 11. |
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| 12. |
- Abend, M., et al.
(författare)
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RENEB Inter-Laboratory Comparison 2021 : The Gene Expression Assay
- 2023
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Ingår i: Radiation Research. - 0033-7587 .- 1938-5404. ; 199:6, s. 598-615
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Tidskriftsartikel (refereegranskat)abstract
- Early and high-throughput individual dose estimates are essential following large-scale radiation exposure events. In the context of the Running the European Network for Biodosimetry and Physical Dosimetry (RENEB) 2021 exercise, gene expression assays were conducted and their corresponding performance for dose-assessment is presented in this publication. Three blinded, coded whole blood samples from healthy donors were exposed to 0, 1.2 and 3.5 Gy X-ray doses (240 kVp, 1 Gy/min) using the X-ray source Yxlon. These exposures correspond to clinically relevant groups of unexposed, low dose (no severe acute health effects expected) and high dose exposed individuals (requiring early intensive medical health care). Samples were sent to eight teams for dose estimation and identification of clinically relevant groups. For quantitative reverse transcription polymerase chain reaction (qRT-PCR) and microarray analyses, samples were lysed, stored at 20°C and shipped on wet ice. RNA isolations and assays were run in each laboratory according to locally established protocols. The time-to-result for both rough early and more precise later reports has been documented where possible. Accuracy of dose estimates was calculated as the difference between estimated and reference doses for all doses (summed absolute difference, SAD) and by determining the number of correctly reported dose estimates that were defined as ±0.5 Gy for reference doses <2.5 Gy and ±1.0 Gy for reference doses >3 Gy, as recommended for triage dosimetry. We also examined the allocation of dose estimates to clinically/diagnostically relevant exposure groups. Altogether, 105 dose estimates were reported by the eight teams, and the earliest report times on dose categories and estimates were 5 h and 9 h, respectively. The coefficient of variation for 85% of all 436 qRT-PCR measurements did not exceed 10%. One team reported dose estimates that systematically deviated several-fold from reported dose estimates, and these outliers were excluded from further analysis. Teams employing a combination of several genes generated about two-times lower median SADs (0.8 Gy) compared to dose estimates based on single genes only (1.7 Gy). When considering the uncertainty intervals for triage dosimetry, dose estimates of all teams together were correctly reported in 100% of the 0 Gy, 50% of the 1.2 Gy and 50% of the 3.5 Gy exposed samples. The order of dose estimates (from lowest to highest) corresponding to three dose categories (unexposed, low dose and highest exposure) were correctly reported by all teams and all chosen genes or gene combinations. Furthermore, if teams reported no exposure or an exposure >3.5 Gy, it was always correctly allocated to the unexposed and the highly exposed group, while low exposed (1.2 Gy) samples sometimes could not be discriminated from highly (3.5 Gy) exposed samples. All teams used FDXR and 78.1% of correct dose estimates used FDXR as one of the predictors. Still, the accuracy of reported dose estimates based on FDXR differed considerably among teams with one team's SAD (0.5 Gy) being comparable to the dose accuracy employing a combination of genes. Using the workflow of this reference team, we performed additional experiments after the exercise on residual RNA and cDNA sent by six teams to the reference team. All samples were processed similarly with the intention to improve the accuracy of dose estimates when employing the same workflow. Re-evaluated dose estimates improved for half of the samples and worsened for the others. In conclusion, this inter-laboratory comparison exercise enabled (1) identification of technical problems and corrections in preparations for future events, (2) confirmed the early and high-throughput capabilities of gene expression, (3) emphasized different biodosimetry approaches using either only FDXR or a gene combination, (4) indicated some improvements in dose estimation with FDXR when employing a similar methodology, which requires further research for the final conclusion and (5) underlined the applicability of gene expression for identification of unexposed and highly exposed samples, supporting medical management in radiological or nuclear scenarios.
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| 13. |
- Almqvist, Catarina, et al.
(författare)
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Cohort profile : Swedish Twin Study on Prediction and Prevention of Asthma (STOPPA)
- 2015
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Ingår i: Twin Research and Human Genetics. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1832-4274 .- 1839-2628.
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Tidskriftsartikel (refereegranskat)abstract
- Asthma is a common childhood disease and several risk factors have been identified, however the impact of genes and environment is not fully understood. The aim of the Swedish Twin study On Prediction and Prevention of Asthma (STOPPA) is to identify environmental (birth characteristics and early life) and genetic (including epigenetic) factors as determinants for asthmatic disease. Based on the Child and Adolescent Twin Study in Sweden (parental interview at 9 or 12 years, N~23,900) and an asthma and/or wheezing algorithm, we identified a sample of monozygotic (MZ) and dizygotic (DZ) same-sexed twin pairs. The twin pairs were identified as asthma concordant (ACC), asthma discordant (ADC) and healthy concordant (HCC). A sample of 9- to 14-year-old twins and their parents were invited to participate in a clinical examination. Background characteristics were collected in questionnaires and obtained from the National Health Registers. A clinical examination was performed to test lung function and capacity (spirometry with reversibility test and exhaled nitric oxide) and collect blood (serology and DNA), urine (metabolites), feces (microbiota) and saliva (cortisol). In total, 376 twin pairs (752 individual twins) completed the study, response rate 52%. All participating twins answered the questionnaire and >90% participated in lung function testing, blood and saliva sampling. This article describes the design, recruitment, data collection, measures, background characteristics as well as ongoing and planned analyses in STOPPA. Potential gains of the study include the identification of biomarkers, the emergence of candidates for drug development and new leads for prevention of asthma and allergic disease.
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| 14. |
- Altenburger, A., et al.
(författare)
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Dimorphism in cryptophytes—The case of Teleaulax amphioxeia/Plagioselmis prolonga and its ecological implications
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:37
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Tidskriftsartikel (refereegranskat)abstract
- Growing evidence suggests that sexual reproduction might be common in unicellular organisms, but observations are sparse. Limited knowledge of sexual reproduction constrains understanding of protist ecology. Although Teleaulax amphioxeia and Plagioselmis prolonga are common marine cryptophytes worldwide, and are also important plastid donors for some kleptoplastic ciliates and dinoflagellates, the ecology and development of these protists are poorly known. We demonstrate that P. prolonga is the haploid form of the diploid T. amphioxeia and describe the seasonal dynamics of these two life stages. The diploid T. amphioxeia dominates during periods of high dissolved inorganic nitrogen (DIN) and low irradiance, temperature, and grazing (winter and early spring), whereas the haploid P. prolonga becomes more abundant during the summer, when DIN is low and irradiance, temperature, and grazing are high. Dimorphic sexual life cycles might explain the success of this species by fostering high genetic diversity and enabling endurance in adverse conditions.
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| 18. |
- Bielecki, Johan, 1982, et al.
(författare)
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Electrospray sample injection for single-particle imaging with x-ray lasers
- 2019
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Ingår i: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 5:5
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Tidskriftsartikel (refereegranskat)abstract
- The possibility of imaging single proteins constitutes an exciting challenge for x-ray lasers. Despite encouraging results on large particles, imaging small particles has proven to be difficult for two reasons: not quite high enough pulse intensity from currently available x-ray lasers and, as we demonstrate here, contamination of the aerosolized molecules by nonvolatile contaminants in the solution. The amount of contamination on the sample depends on the initial droplet size during aerosolization. Here, we show that, with our electrospray injector, we can decrease the size of aerosol droplets and demonstrate virtually contaminant-free sample delivery of organelles, small virions, and proteins. The results presented here, together with the increased performance of next-generation x-ray lasers, constitute an important stepping stone toward the ultimate goal of protein structure determination from imaging at room temperature and high temporal resolution.
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| 19. |
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| 20. |
- Brooks, M., et al.
(författare)
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Molecular Impurities as a Realization of Anyons on the Two-Sphere
- 2021
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Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 126:1
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Tidskriftsartikel (refereegranskat)abstract
- Studies on the experimental realization of two-dimensional anyons in terms of quasiparticles have been restricted, so far, to only anyons on the plane. It is known, however, that the geometry and topology of space can have significant effects on quantum statistics for particles moving on it. Here, we have undertaken the first step toward realizing the emerging fractional statistics for particles restricted to move on the sphere instead of on the plane. We show that such a model arises naturally in the context of quantum impurity problems. In particular, we demonstrate a setup in which the lowest-energy spectrum of two linear bosonic or fermionic molecules immersed in a quantum many-particle environment can coincide with the anyonic spectrum on the sphere. This paves the way toward the experimental realization of anyons on the sphere using molecular impurities. Furthermore, since a change in the alignment of the molecules corresponds to the exchange of the particles on the sphere, such a realization reveals a novel type of exclusion principle for molecular impurities, which could also be of use as a powerful technique to measure the statistics parameter. Finally, our approach opens up a simple numerical route to investigate the spectra of many anyons on the sphere. Accordingly, we present the spectrum of two anyons on the sphere in the presence of a Dirac monopole field.
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| 21. |
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| 22. |
- Elia, M, et al.
(författare)
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Enteral (oral or tube administration) nutritional support and eicosapentaenoic acid in patients with cancer: a systematic review.
- 2006
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Ingår i: International journal of oncology. - 1019-6439. ; 28:1, s. 5-23
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this systematic review was to determine the efficacy and potential benefits of enteral nutritional support [oral nutritional supplements (ONS) or enteral tube feeding (ETF)], and eicosapentaenoic acid (EPA, free acid, ethyl esters or fish oil; provided as capsules or enriched ONS or ETF) in patients with cancer. Clinical studies were identified using electronic databases, and studies were selected according to predetermined criteria. For each treatment modality (chemo/radiotherapy, surgery, and palliative care), the comparisons of interest were nutritional support vs. routine care (no nutritional support), EPA supplement (capsule or enriched ONS or ETF) vs. routine care (no supplement or standard supplement), ETF vs. parenteral nutrition (PN). The reviewed outcomes were dietary intake, anthropometry, clinical (mortality, length of hospital stay, complications, and quality of life) and haematological/biochemical (white blood cell count, serum transferrin and albumin, CD3-positive lymphocytes, and inflammatory markers). Meta-analyses were performed where possible. In patients undergoing radiotherapy, meta-analysis showed that ONS significantly increase dietary intake (381 kcal/day, 95% CI 193 to 569 in 3 RCTs) compared to routine care. In patients undergoing surgery, meta-analyses showed that ETF results in a significantly shorter length of hospital stay (1.72 fewer days, 95% CI 0.90 to 2.54 in 8 RCTs), lower incidence of any complications (OR 0.62, 95% CI 0.50 to 0.77 in 4 RCTs) and infectious complications (OR 0.67, 95% CI 0.55 to 0.82 in 11 RCTs) and lower sepsis scores (2.21 points, 95% CI 1.49 to 2.92 in 2 RCTs), but no difference in mortality (OR 0.72, 95% CI 0.40 to 1.29 in 7 RCTs) compared to PN. There was also no difference in mortality between ONS or ETF vs. routine care in patients undergoing chemotherapy/radiotherapy (OR 1.00, 95% CI 0.62-1.61 in 4 RCTs) or surgery (OR 2.44, 95% CI 0.75 to 7.95 in 4 RCTs). Individual studies of EPA supplementation as capsules showed improvements in survival, complications and inflammatory markers in patients undergoing bone marrow transplant (BMT). In palliative care patients receiving EPA-enriched ONS or capsules, there were inconsistent positive effects on survival and quality of life. In those undergoing surgery, EPA-enriched ETF had no effect. Further research is required to elucidate the clinical efficacy of enteral nutrition support, including the potential benefits of EPA supplementation, in patients with cancer.
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| 23. |
- Eriksson, Britt-Marie, et al.
(författare)
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Diagnosis of pulmonary infections in immunocompromised patients by fiber-optic bronchoscopy with bronchoalveolar lavage and serology
- 1996
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 28:5, s. 479-485
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Tidskriftsartikel (refereegranskat)abstract
- Fiber-optic bronchoscopy (FOB) and bronchoalveolar lavage (BAL) were performed on 67 occasions in 57 immunocompromised patients with symptoms consistent with pulmonary infection. Diagnosis was achieved more often in renal transplant patients than in patients with hematological malignancies (85% versus 28%). Culture (bacteria, virus, fungi), staining and microscopy (bacteria, fungi, Pneumocystis carinii (PC)) and antigen detection by indirect immunofluorescence (cytomegalovirus (CMV), respiratory viruses, PC, Legionella) were used for diagnosis. On 20 occasions transbronchial biopsies with histopathologic examination were performed. In addition, serology comprising the herpes group (HHV-6) and respiratory viruses was done. A microbial diagnosis was obtained on 45% of occasions. The most common pathogens found were CMV (31%) and PC (25%). On 22 (33%) occasions a rapid diagnosis of 1 or more microbial agents was obtained within 24 h by conventional staining or indirect immunofluorescence. The clinical relevance of findings of CMV, HHV-6, and Epstein-Barr virus in BAL by polymerase chain detection on 18, 6 and 3 occasions is discussed. On 4 occasions pathogenic bacteria were found. It was not possible to relate findings of coagulase-negative staphylococci, alpha-streptococci and Candida albicans to the pulmonary infection.
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| 24. |
- Godhe, Anna, 1967, et al.
(författare)
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Physical barriers and environmental gradients cause spatial and temporal genetic differentiation of an extensive algal bloom
- 2016
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Ingår i: Journal of Biogeography. - : John Wiley & Sons. - 0305-0270 .- 1365-2699. ; 43:6, s. 1130-1142
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To test if a phytoplankton bloom is panmictic, or whether geographical and environmental factors cause spatial and temporal genetic structure.Location: Baltic Sea.Method: During four cruises, we isolated clonal strains of the diatom Skeletonema marinoifrom 9 to 10 stations along a 1132 km transect and analysed the genetic structure using eight microsatellites. Using F-statistics and Bayesian clustering analysis we determined if samples were significantly differentiated. A seascape approach was applied to examine correlations between gene flow and oceanographic connectivity, and combined partial Mantel test and RDA based variation partitioning to investigate associations with environmental gradients.Results: The bloom was initiated during the second half of March in the southern and the northern- parts of the transect, and later propagated offshore. By mid-April the bloom declined in the south, whereas high phytoplankton biomass was recorded northward. We found two significantly differentiated populations along the transect. Genotypes were significantly isolated by distance and by the south–north salinity gradient, which illustrated that the effects of distance and environment were confounded. The gene flow among the sampled stations was significantly correlated with oceanographic connectivity. The depletion of silica during the progression of the bloom was related to a temporal population genetic shift.Main conclusions: A phytoplankton bloom may propagate as a continuous cascade and yet be genetically structured over both spatial and temporal scales. The Baltic Sea spring bloom displayed strong spatial structure driven by oceanographic connectivity and geographical distance, which was enhanced by the pronounced salinity gradient. Temporal transition of conditions important for growth may induce genetic shifts and different phenotypic strategies, which serve to maintain the bloom over longer periods.
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