| 1. |
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| 2. |
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| 3. |
- Cirenajwis, Helena, et al.
(author)
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Molecular stratification of metastatic melanoma using gene expression profiling: prediction of survival outcome and benefit from molecular targeted therapy.
- 2015
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:14, s. 12297-12309
-
Journal article (peer-reviewed)abstract
- Melanoma is currently divided on a genetic level according to mutational status. However, this classification does not optimally predict prognosis. In prior studies, we have defined gene expression phenotypes (high-immune, pigmentation, proliferative and normal-like), which are predictive of survival outcome as well as informative of biology. Herein, we employed a population-based metastatic melanoma cohort and external cohorts to determine the prognostic and predictive significance of the gene expression phenotypes. We performed expression profiling on 214 cutaneous melanoma tumors and found an increased risk of developing distant metastases in the pigmentation (HR, 1.9; 95% CI, 1.05-3.28; P=0.03) and proliferative (HR, 2.8; 95% CI, 1.43-5.57; P=0.003) groups as compared to the high-immune response group. Further genetic characterization of melanomas using targeted deep-sequencing revealed similar mutational patterns across these phenotypes. We also used publicly available expression profiling data from melanoma patients treated with targeted or vaccine therapy in order to determine if our signatures predicted therapeutic response. In patients receiving targeted therapy, melanomas resistant to targeted therapy were enriched in the MITF-low proliferative subtype as compared to pre-treatment biopsies (P=0.02). In summary, the melanoma gene expression phenotypes are highly predictive of survival outcome and can further help to discriminate patients responding to targeted therapy.
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| 4. |
- Ekblom Bak, Elin, 1981-, et al.
(author)
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Accelerometer derived physical activity patterns in 27.890 middle‐aged adults : The SCAPIS cohort study
- 2022
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In: Scandinavian Journal of Medicine and Science in Sports. - : John Wiley & Sons. - 0905-7188 .- 1600-0838. ; 32:5, s. 866-880
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Journal article (peer-reviewed)abstract
- The present study aims to describe accelerometer-assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle-aged men and women, and to study differences between subgroups of socio-demographic, socio-economic, and lifestyle-related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle-aged men and women with at least four days of valid hip-worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X-BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All-year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty-eight percent was defined as having an “at-risk” behavior, which included both high sedentary time and low vigorous PA. In this large population-based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice.
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| 5. |
- Eriksson, Daniel, et al.
(author)
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Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS1
- 2018
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 103:1, s. 179-186
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Journal article (peer-reviewed)abstract
- Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.
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| 6. |
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| 7. |
- Harbst, Katja, et al.
(author)
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Multiregion whole-exome sequencing uncovers the genetic evolution and mutational heterogeneity of early-stage metastatic melanoma
- 2016
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In: Cancer Research. - 0008-5472. ; 76:16, s. 4765-4774
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Journal article (peer-reviewed)abstract
- Cancer genome sequencing has shed light on the underlying genetic aberrations that drive tumorigenesis. However, current sequencing-based strategies, which focus on a single tumor biopsy, fail to take into account intratumoral heterogeneity. To address this challenge and elucidate the evolutionary history of melanoma, we performed whole-exome and transcriptome sequencing of 41 multiple melanoma biopsies from eight individual tumors. This approach revealed heterogeneous somatic mutations in the range of 3%-38% in individual tumors. Known mutations in melanoma drivers BRAF and NRAS were always ubiquitous events. Using RNA sequencing, we found that the majority of mutations were not expressed or were expressed at very low levels, and preferential expression of a particular mutated allele did not occur frequently. In addition, we found that the proportion of ultraviolet B (UVB) radiation-induced C>T transitions differed significantly (P <0.001) between early and late mutation acquisition, suggesting that different mutational processes operate during the evolution of metastatic melanoma. Finally, clinical history reports revealed that patients harboring a high degree of mutational heterogeneity were associated with more aggressive disease progression. In conclusion, our multiregion tumor-sequencing approach highlights the genetic evolution and non-UVB mutational signatures associated with melanoma development and progression, and may provide a more comprehensive perspective of patient outcome.
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| 8. |
- Karlsson, Anna K, et al.
(author)
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Mutational and gene fusion analyses of primary large cell and large cell neuroendocrine lung cancer.
- 2015
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In: Oncotarget. - 1949-2553. ; 6:26, s. 22028-22037
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Journal article (peer-reviewed)abstract
- Large cell carcinoma with or without neuroendocrine features (LCNEC and LC, respectively) constitutes 3-9% of non-small cell lung cancer but is poorly characterized at the molecular level. Herein we analyzed 41 LC and 32 LCNEC (including 15 previously reported cases) tumors using massive parallel sequencing for mutations in 26 cancer-related genes and gene fusions in ALK, RET, and ROS1. LC patients were additionally subdivided into three immunohistochemistry groups based on positive expression of TTF-1/Napsin A (adenocarcinoma-like, n = 24; 59%), CK5/P40 (squamous-like, n = 5; 12%), or no marker expression (marker-negative, n = 12; 29%). Most common alterations were TP53 (83%), KRAS (22%), MET (12%) mutations in LCs, and TP53 (88%), STK11 (16%), and PTEN (13%) mutations in LCNECs. In general, LCs showed more oncogene mutations compared to LCNECs. Immunomarker stratification of LC revealed oncogene mutations in 63% of adenocarcinoma-like cases, but only in 17% of marker-negative cases. Moreover, marker-negative LCs were associated with inferior overall survival compared with adenocarcinoma-like tumors (p = 0.007). No ALK, RET or ROS1 fusions were detected in LCs or LCNECs. Together, our molecular analyses support that LC and LCNEC tumors follow different tumorigenic paths and that LC may be stratified into molecular subgroups with potential implications for diagnosis, prognostics, and therapy decisions.
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| 9. |
- Lauss, Martin, et al.
(author)
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Genome-Wide DNA Methylation Analysis in Melanoma Reveals the Importance of CpG Methylation in MITF Regulation.
- 2015
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In: Journal of Investigative Dermatology. - : Elsevier BV. - 1523-1747 .- 0022-202X. ; 135:7, s. 1820-1828
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Journal article (peer-reviewed)abstract
- The microphthalmia-associated transcription factor (MITF) is a key regulator of melanocyte development and a lineage-specific oncogene in melanoma; a highly lethal cancer known for its unpredictable clinical course. MITF is regulated by multiple intracellular signaling pathways although the exact mechanisms that determine MITF expression and activity remain incompletely understood. In this study, we obtained genome-wide DNA methylation profiles from 50 stage IV melanomas, normal melanocytes, keratinocytes and dermal fibroblasts, and utilized The Cancer Genome Atlas (TCGA) data for experimental validation. By integrating DNA methylation and gene expression data we found that hypermethylation of MITF and its co-regulated differentiation pathway genes, corresponded to decreased gene expression levels. In cell lines with a hypermethylated MITF-pathway, over-expression of MITF did not alter the expression level or methylation status of the MITF pathway genes. In contrast however, demethylation treatment of these cell lines induced MITF-pathway activity, confirming that gene-regulation was controlled via methylation. The discovery that the activity of the master regulator of pigmentation, MITF, and its downstream targets may be regulated by hypermethylation has significant implications for understanding the development and evolvement of melanoma.Journal of Investigative Dermatology accepted article preview online, 23 February 2015. doi:10.1038/jid.2015.61.
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| 10. |
- Lauss, Martin, et al.
(author)
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Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma
- 2017
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
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Journal article (peer-reviewed)abstract
- Adoptive T-cell therapy (ACT) is a highly intensive immunotherapy regime that has yielded remarkable response rates and many durable responses in clinical trials in melanoma; however, 50-60% of the patients have no clinical benefit. Here, we searched for predictive biomarkers to ACT in melanoma. Whole exome-and transcriptome sequencing and neoantigen prediction were applied to pre-treatment samples from 27 patients recruited to a clinical phase I/II trial of ACT in stage IV melanoma. All patients had previously progressed on other immunotherapies. We report that clinical benefit is associated with significantly higher predicted neoantigen load. High mutation and predicted neoantigen load are significantly associated with improved progression-free and overall survival. Further, clinical benefit is associated with the expression of immune activation signatures including a high MHC-I antigen processing and presentation score. These results improve our understanding of mechanisms behind clinical benefit of ACT in melanoma.
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| 11. |
- Lindquist, Kajsa Ericson, et al.
(author)
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Clinical framework for next generation sequencing based analysis of treatment predictive mutations and multiplexed gene fusion detection in non-small cell lung cancer
- 2017
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In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 8:21, s. 34796-34810
-
Journal article (peer-reviewed)abstract
- Precision medicine requires accurate multi-gene clinical diagnostics. We describe the implementation of an Illumina TruSight Tumor (TST) clinical NGS diagnostic framework and parallel validation of a NanoString RNA-based ALK, RET, and ROS1 gene fusion assay for combined analysis of treatment predictive alterations in non-small cell lung cancer (NSCLC) in a regional healthcare region of Sweden (Scandinavia). The TST panel was clinically validated in 81 tumors (99% hotspot mutation concordance), after which 533 consecutive NSCLCs were collected during one-year of routine clinical analysis in the healthcare region (~90% advanced stage patients). The NanoString assay was evaluated in 169 of 533 cases. In the 533-sample cohort 79% had 1-2 variants, 12% >2 variants and 9% no detected variants. Ten gene fusions (five ALK, three RET, two ROS1) were detected in 135 successfully analyzed cases (80% analysis success rate). No ALK or ROS1 FISH fusion positive case was missed by the NanoString assay. Stratification of the 533-sample cohort based on actionable alterations in 11 oncogenes revealed that 66% of adenocarcinomas, 13% of squamous carcinoma (SqCC) and 56% of NSCLC not otherwise specified harbored ≥1 alteration. In adenocarcinoma, 10.6% of patients (50.3% if including KRAS) could potentially be eligible for emerging therapeutics, in addition to the 15.3% of patients eligible for standard EGFR or ALK inhibitors. For squamous carcinoma corresponding proportions were 4.4% (11.1% with KRAS) vs 2.2%. In conclusion, multiplexed NGS and gene fusion analyses are feasible in NSCLC for clinical diagnostics, identifying notable proportions of patients potentially eligible for emerging molecular therapeutics.
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| 12. |
- Maria, Tillquist, et al.
(author)
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Dare to ask children as relatives! A qualitative study about female teenagers’ experiences of losing a parent to cancer.
- 2016
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In: Home Health Care Management & Practice. - : SAGE Publications. - 1084-8223 .- 1552-6739. ; 28:2, s. 94-100
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Journal article (peer-reviewed)abstract
- Nurses must pay attention to teenager altered lives when a parent receives treatment for cancer. The aim of this study was to describe female teenagers’ experiences of losing a parent to cancer. Blogs written by girls (13-19 years) were utilized and analyzed from a qualitative perspective. Four categories were highlighted from the analysis: sadness, fear, anger, and comfort. Blogs served as a tool for gathering strength for teenagers in their difficult circumstances. The results show that female teenagers need information and support through their parent’s end-of-life care to be able to move on after the traumatic experience. Support needs to be in line with the children’s individual needs.
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| 13. |
- Norris, Daniel H., et al.
(author)
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On the diversity and richness of understory bryophytes at Nectandra Cloud Forest Reserve, Costa Rica
- 2017
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In: Biodiversity Data Journal. - 1314-2836. ; 5:1
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Journal article (peer-reviewed)abstract
- Background A survey of the understory bryophytes in the Nectandra Cloud Forest Preserve yielded 1083 specimens distributed among 55 families, represented by 74 genera of mosses, 75 genera of liverworts and 3 of hornworts. We studied and analyzed the bryophytic distribution on six types of substrates: 1) corticolous, 2) epiphyllous, 3) saxicolous, 4) terricolous, 5) aquatic and 6) lignicolous. The richness and composition of bryophyte genera are compared to those of other previous bryophyte surveys from 4 other sites with different oceanic exposures, climatic and geographic conditions in Costa Rica. New information This is a report of the first extensive general survey of bryophytes at the Nectandra Reserve, a premontane cloud forest located on the Atlantic slope of Costa Rica, an area much less studied compared to the Monteverde cloud forest on the Pacific slope.
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| 14. |
- Phung, Bengt, et al.
(author)
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The X-Linked DDX3X RNA Helicase Dictates Translation Reprogramming and Metastasis in Melanoma
- 2019
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 27:12, s. 7-3586
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Journal article (peer-reviewed)abstract
- The X-linked DDX3X gene encodes an ATP-dependent DEAD-box RNA helicase frequently altered in various human cancers, including melanomas. Despite its important roles in translation and splicing, how DDX3X dysfunction specifically rewires gene expression in melanoma remains completely unknown. Here, we uncover a DDX3X-driven post-transcriptional program that dictates melanoma phenotype and poor disease prognosis. Through an unbiased analysis of translating ribosomes, we identified the microphthalmia-associated transcription factor, MITF, as a key DDX3X translational target that directs a proliferative-to-metastatic phenotypic switch in melanoma cells. Mechanistically, DDX3X controls MITF mRNA translation via an internal ribosome entry site (IRES) embedded within the 5' UTR. Through this exquisite translation-based regulatory mechanism, DDX3X steers MITF protein levels dictating melanoma metastatic potential in vivo and response to targeted therapy. Together, these findings unravel a post-transcriptional layer of gene regulation that may provide a unique therapeutic vulnerability in aggressive male melanomas.
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| 15. |
- Rosengren, Frida, et al.
(author)
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Balance between inbreeding and outcrossing in a nannandrous species, the moss Homalothecium lutescens.
- 2016
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In: Heredity. - : Springer Science and Business Media LLC. - 1365-2540 .- 0018-067X. ; 116:1, s. 107-113
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Journal article (peer-reviewed)abstract
- Epiphytic dwarf males on the females present a possible solution to the problem of short fertilization distances in mosses. However, leptokurtic spore dispersal makes dwarf males likely to be closely related to their host shoot, with an accompanying risk of inbreeding. The capacity of a female to harbour a high number of different dwarf males suggests that there may be mechanisms in place that counteract inbreeding, such as polyandry and post-fertilization selection. We have genotyped sporophytes, female host shoots and dwarf males in four populations of the moss Homalothecium lutescens. We found no evidence of selective sporophyte abortion based on level of heterozygosity. The occurrence of entirely homozygous sporophytes together with significantly positive inbreeding coefficients in three of the populations (mean FIS between 0.48 and 0.64) suggest frequent mother-son mating events. However, 23% of all sampled sporophytes had a higher level of heterozygosity compared with the mean expected heterozygosity at the population level. Polyandry was frequent, on average 59% of the sporophytes on a female shoot were sired by distinct fathers. In conclusion, sporadic fertilizations by dwarf males originating from nonhost female shoots appear to counteract strong inbreeding.Heredity advance online publication, 2 September 2015; doi:10.1038/hdy.2015.79.
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| 16. |
- Rosengren, Frida
(author)
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Genetic variation and sexual reproduction in a moss with dwarf males, Homalothecium lutescens
- 2015
-
Doctoral thesis (other academic/artistic)abstract
- Dwarf males occur in many unrelated groups of organisms. Among land plants they are unique to mosses. Moss dwarf males originate from male spores that land and germinate on the female where their final size is restricted to a few mm. Fertilization in mosses occur over short distances with swimming spermatozoids. Having the males growing as tiny epiphytes on the females facilitates fertilization, as the male and female sexual organs are positioned more closely together. Many things are unknown about the moss dwarf males. In this thesis we investigate dispersal and establishment of dwarf males and female shoots within populations of a moss with dwarf males, Homalothecium lutescens. We also investigate regulation of spore germination on the female shoots. Finally, we investigate population genetic variation and structure as well as gene flow and levels of inbreeding in populations with high abundance of dwarf males. Our results confirm that the presence of dwarf males increase the level of fertilization. Dwarf males are often more closely related to their host shoot, which indicates that spores are mostly dispersed locally. In accordance, we showed that inbreeding levels were generally high. However, polyandry together with sporadic fertilization of dwarf males originating from non-host females appears to maintain the genetic variation on relatively high levels. We could not find any mechanisms that prevent or limit inbreeding, but as the significance of inbreeding depression in mosses is unclear, it is difficult to draw any conclusions regarding potential consequences. Dwarf males and females appear to follow two different recruitment models. Female shoots follow a repeated recruitment model where new females are rarely but continuously recruited from spores. Dwarf males on the other hand, follow a metapopulation or source-sink dynamics. Local dwarf male populations may occasionally go extinct (as a result of their individual short life span and drought sensitivity), but the high dispersal potential of spores and the ability of dwarf males to establish in high numbers in mature colonies, enables re-colonization when conditions improve. We also showed that spores from the moss Isothecium alopecuroides (another moss with dwarf males) could not develop into dwarf males on shoots of H. lutescens. Prevention of spore germination in mature colonies has been shown before and could be a mechanism to prevent hybridization or reduce competition. In contrast, spores from the sister species Homalothecium sericeum were able to develop into fertile dwarf males on shoots of H. lutescens. This result suggests a previously unexplored hybridization pathway between closely related species and could alter the way we view reproductive isolation in mosses.
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| 17. |
- Rosengren, Frida, et al.
(author)
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Genetic variation in the moss Homalothecium lutescens in relation to habitat age and structure
- 2013
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In: Botany. - : Canadian Science Publishing. - 1916-2804 .- 1916-2790. ; 91:7, s. 431-441
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Journal article (peer-reviewed)abstract
- Relationships between genetic (allozyme) variation and landscape age and structure were investigated in 17 calcareous grassland demes of the moss Homalothecium lutescens (Hedw.) H. Rob. on the Baltic island of Oland. Mean within-deme gene diversity (H-S = 0.152) was moderate compared with other bryophyte studies, and the between-deme proportion of the total diversity (G(ST) = 0.100, Jost's D = 0.011) was low but significantly different from zero. Clonal mixing, measured as the proportion of two adjacent shoots having different haplotypes, was relatively high (mean 0.32 over all demes). HS was higher in old grassland fragments, but negatively related to vascular plant species richness. Allelic richness (A) was positively associated with the area of old (>= 280 years) grassland in the surroundings: although demes in old grasslands are genetically more variable than those in younger grasslands, proximity to large areas of old grassland may promote genetic variability even in younger grassland demes. The importance of management continuity for species diversity has been stressed in many earlier grassland studies. Here, we conclude that grassland fragments with a long history of grazing continuity are also positively associated with variability at within-species level, as exemplified by the bryophyte H. lutescens.
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| 18. |
- Rosengren, Frida, et al.
(author)
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Population structure and genetic diversity in the nannandrous moss Homalothecium lutescens: does the dwarf male system facilitate gene flow?
- 2015
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In: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 15
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Journal article (peer-reviewed)abstract
- Nannandry is a sexual system where males ("dwarf males") are much smaller than the conspecific females. Dwarf males occur in a wide range of unrelated organisms but the evolutionary advantages of this condition are poorly understood. The dwarf male sexual system results in differences in the mode of dispersal and establishment as well as the life span between males and females. Such differences must have profound effects on the population dynamics and genetic structures. We have studied four populations of the nannandrous moss Homalothecium lutescens in southern Sweden. We genotyped dwarf males and female shoots with the aim of describing the genetic diversity and structure of the populations.
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| 19. |
- Rosengren, Frida, et al.
(author)
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Selective spore germination on shoots of Homalothecium lutescens, a moss with dwarf males.
- 2015
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In: Biology letters. - : The Royal Society. - 1744-9561 .- 1744-957X. ; 11:7
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Journal article (peer-reviewed)abstract
- Spores from three bryophyte species with dwarf males (Homalothecium lutescens, Homalothecium sericeum and Isothecium alopecuroides) were sown on shoots of H. lutescens in vitro. After 10 months, presence and fertility of dwarf plants were scored. Spores of the more distantly related I. alopecuroides were unable to develop into dwarf plants on H. lutescens. Spores of both H. lutescens and H. sericeum developed into dwarf plants. In fact, dwarf plants of H. sericeum were both more abundant and more often fertile than those of H. lutescens. The ability of H. sericeum spores to develop into dwarf males on shoots of H. lutescens suggests a possible pathway for hybridization between the two species. On the other hand, the inability of I. alopecuroides to develop into dwarf males on shoots of H. lutescens suggests that regulation of spore germination and dwarf male development on host shoots is associated with the degree of relatedness between species.
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| 20. |
- Rosengren, Frida, et al.
(author)
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Sexual reproduction in the phyllodioicous bryophyte Homalothecium lutescens (Hedw.) H.Rob. in relation to habitat age, growth conditions and genetic variation
- 2014
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In: Journal of Bryology. - 1743-2820. ; 36:3, s. 200-208
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Journal article (peer-reviewed)abstract
- Sporophyte production and female fertility were investigated in seventeen calcareous grassland demes of the moss Homalothecium lutescens (Hedw.) H.Rob. on the Baltic island of Öland, with the aim of understanding the relationships between sexual reproduction, habitat age, genetic variation and factors related to growth conditions. The overall proportion of fertile female shoots (with perichaetia) was 35%. Fertility status at the level of individual shoots was positively associated with shoot length and density, while within deme fertility was positively associated with bush cover. There was no association between female fertility and habitat age, genetic diversity (HS) or allelic richness. Out of 1344 investigated shoots, only two were normal-sized fertile males. Dwarf males were also extremely rare, and found almost exclusively on shoots with sporophytes. Few sporophytes were observed (in the two demes with highest fertility and bush cover). No relationship between genetic variation and the frequency of sporophytes and males was found. The lack of a relationship between sexual reproduction and genetic variation suggests that sexual reproduction may not occur in the same grassland fragments as the recruitment of new clones (from spores or vegetative fragments). The majority of the dry, open grassland habitats, where H. lutescens is typically found in the study area, appear to be suboptimal for both dwarf males and fertilization. Sexual reproduction is more likely to occur in shaded (although grazed) grassland patches, where moisture levels are likely to be higher and the moss colonies are generally more vigorous.
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| 21. |
- Rosengren, Frida, et al.
(author)
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The adaptive background of nannandry: dwarf male distribution and fertilization in the moss Homalothecium lutescens
- 2014
-
In: Biological Journal of the Linnean Society. - : Oxford University Press (OUP). - 0024-4066. ; 113:1, s. 74-84
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Journal article (peer-reviewed)abstract
- Dwarf males (nannandry) occur in many unrelated, mostly aquatic, groups of organisms. Among land plants they are unique to bryophytes. In this study our aim was to explain variation in frequency of dwarf males and fertilization within populations in the moss Homalothecium lutescens. We compared parameters related to dwarf male presence and sporophyte production in 90 colonies from three localities. Dwarf male density was positively associated with colony moisture at two of the localities, suggesting increased spore germination and dwarf male survival with moist conditions. At one of these localities, dwarf male density was also positively associated with the presence of perichaetia (female sexual branches). Dwarf male density and fertilization frequency were positively associated in two of the localities. Furthermore, in one population, fertilization was also positively associated with canopy cover, which could be attributed to improved nutrient status as a result of throughfall, increased sperm-dispersal efficiency because of larger water drops, or more favourable moisture conditions as a result of shading. Nannandry thus appears to strongly reduce the problem of short fertilization distances in bryophytes, but the presence of water is still critical because the dwarf males are dependent on a certain level of humidity for recruitment and/or development. (C) 2014 The Linnean Society of London,
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| 22. |
- Sanna, Adriana, et al.
(author)
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DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype
- 2022
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In: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 7:19
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Journal article (peer-reviewed)abstract
- Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, MITF and SOX10, important in melanoma development and progression have been implicated in this process. In this study we describe that loss of MITF is associated with a distinct transcriptional program, MITF promoter hypermethylation and poor patient survival in metastatic melanoma. From a comprehensive collection of melanoma cell lines, we observed that MITF methylated cultures were subdivided in two distinct subtypes. Examining mRNA levels of neural crest associated genes we found that one subtype had lost the expression of several lineage genes including SOX10. Intriguingly, SOX10 loss was associated with SOX10 gene promoter hypermethylation and distinct phenotypic and metastatic properties. Depletion of SOX10 in MITF methylated melanoma cells using CRISPR/Cas9 confirmed these findings. In conclusion, this study describes the significance of melanoma state and the underlying functional properties explaining the aggressiveness of such states.
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| 23. |
- Sanna, Adriana, et al.
(author)
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DNA promoter hypermethylation of melanocyte lineage genes determines melanoma phenotype.
- 2022
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In: JCI insight. - : The American Society for Clinical Investigation. - 2379-3708. ; 7:19
-
Journal article (peer-reviewed)abstract
- Cellular stress contributes to the capacity of melanoma cells to undergo phenotype switching into highly migratory and drug-tolerant dedifferentiated states. Such dedifferentiated melanoma cell states are marked by loss of melanocyte-specific gene expression and increase of mesenchymal markers. Two crucial transcription factors, microphthalmia-associated transcription factor (MITF) and SRY-box transcription factor 10 (SOX10), important in melanoma development and progression, have been implicated in this process. In this study we describe that loss of MITF is associated with a distinct transcriptional program, MITF promoter hypermethylation, and poor patient survival in metastatic melanoma. From a comprehensive collection of melanoma cell lines, we observed that MITF-methylated cultures were subdivided in 2 distinct subtypes. Examining mRNA levels of neural crest-associated genes, we found that 1 subtype had lost the expression of several lineage genes, including SOX10. Intriguingly, SOX10 loss was associated with SOX10 gene promoter hypermethylation and distinct phenotypic and metastatic properties. Depletion of SOX10 in MITF-methylated melanoma cells using CRISPR/Cas9 supported these findings. In conclusion, this study describes the significance of melanoma state and the underlying functional properties explaining the aggressiveness of such states.
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| 24. |
- Sanna, Adriana, et al.
(author)
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Tumor genetic heterogeneity analysis of chronic sun-damaged melanoma
- 2020
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In: Pigment Cell & Melanoma Research. - : Wiley. - 1755-148X .- 1755-1471. ; 33:3, s. 480-489
-
Journal article (peer-reviewed)abstract
- Chronic sun-damaged (CSD) melanoma represents 10%-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p < .01, Fisher's exact test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with >95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.
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| 25. |
- Sanna, Adriana, et al.
(author)
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Tumor genetic heterogeneity analysis of chronic sun-damaged melanoma.
- 2020
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In: Pigment cell & melanoma research. - : Wiley-Blackwell. - 1755-148X. ; 33:3, s. 480-489
-
Journal article (peer-reviewed)abstract
- Chronic sun-damaged (CSD) melanoma represents 10%-20% of cutaneous melanomas and is characterized by infrequent BRAF V600E mutations and high mutational load. However, the order of genetic events or the extent of intra-tumor heterogeneity (ITH) in CSDhigh melanoma is still unknown. Ultra-deep targeted sequencing of 40 cancer-associated genes was performed in 72 in situ or invasive CMM, including 23 CSDhigh cases. In addition, we performed whole exome and RNA sequencing on multiple regions of primary tumor and multiple in-transit metastases from one CSDhigh melanoma patient. We found no significant difference in mutation frequency in melanoma-related genes or in mutational load between in situ and invasive CSDhigh lesions, while this difference was observed in CSDlow lesions. In addition, increased frequency of BRAF V600K, NF1, and TP53 mutations (p < .01, Fisher's exact test) was found in CSDhigh melanomas. Sequencing of multiple specimens from one CSDhigh patient revealed strikingly limited ITH with >95% shared mutations. Our results provide evidence that CSDhigh and CSDlow melanomas are distinct molecular entities that progress via different genetic routes.
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| 26. |
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| 27. |
- Tyler, Torbjörn, et al.
(author)
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Nu startar projekt Skånes Mossor!
- 2007
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In: Botaniska Notiser. - 0006-8195. ; 140:2, s. 1-6
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Journal article (peer-reviewed)abstract
- The Lund Botanical Society 2007-03-23 decided to launch a project with the following aims: 1) to map the frequency and distribution of all bryophytes in the province of Skåne, southernmost Sweden, thereby making way for future studies of changes in the flora, 2) to find and document as many sites as possible for nationally and regionally rare or endangered bryophytes and initiate conservation actions at these sites, 3) to increase our knowledge of the ecological demands of individual taxa, and 4) to enhance the level of knowledge concerning bryophytes among both amateur botanists and professional nature conservationists. The province has been divided into 534 5 x 5 km grid-squares. The central square kilometre within each grid-square will be surveyed and the result used for unbiased estimates of the frequency of each taxon. In addition, within each grid-square, a variable number of special areas which may be presumed to have a rich or unusual bryophyte flora have been preselected for the survey. Additional areas may be selected by the recorders themselves, but the ultimate goal is not to survey the grid-square as a whole. A special determination key and nomenclatural check-list to all 658 taxa hithereto known from the province, as well as various instructions and forms for the volonteer recorders, have been made available on the Internet and a central database with an Internet interface is under way. Various kinds of courses have been initiated with the aim of educating future recorders. The aim is to survey all grid-squares during a 20 year period and the project is now calling for support from bryologists world-wide.
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| 28. |
- Tyler, Torbjörn, et al.
(author)
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Projekt Skånes Mossor 2008-2013 - en deltidsrapport
- 2014
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In: Nordic Journal of Botany. - 0107-055X. ; 147:2, s. 1-32
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Journal article (peer-reviewed)abstract
- About 25% of the 531 5x5 km grid squares have been investigated during the six first years of the ongoing survey of the bryophyte flora of the province of Skåne, c. 50 persons have participated and 65,539 records and 21,135 vouchers have been collected. Of the 687 taxa that have ever been reported from the province, 591 have been recorded since 1995 and 34 have been found as new to the province since then. In this part-time report, the records and our present knowledge about each taxon ever found in the province are briefly summarized and it is concluded that our knowledge of the bryophyte flora of the province has increased multifold during these six years of intense surveying.
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| 29. |
- Åberg, Maria A I, 1972, et al.
(author)
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Selective introduction of antisense oligonucleotides into single adult CNS progenitor cells using electroporation demonstrates the requirement of STAT3 activation for CNTF-induced gliogenesis
- 2001
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In: Mol Cell Neurosci. - : Elsevier BV. ; 17:3, s. 426-43
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Journal article (peer-reviewed)abstract
- We have developed a novel method in which antisense DNA is selectively electroporated into individual adult neural progenitor cells. By electroporation of antisense oligonucleotides against signal transducer and activator of transcription 3 (STAT3) we demonstrate that ciliary neurotrophic factor (CNTF) is an instructive signal for astroglial type 2 cell fate specifically mediated via activation of STAT3. Activation of the mitogen-activated protein kinase (MAPK) signaling pathway induced only a transient increase in glial fibrillary acidic protein (GFAP) expression, and inhibition of this signaling pathway did not block the induction by CNTF of glial differentiation in progenitor cells. In addition we show that microelectroporation is a new powerful method for introducing antisense agents into single cells in complex cellular networks.
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