| 1. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Flores-Langarica, Adriana, et al.
(författare)
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Intestinal CD103+CD11b+ cDC2 conventional dendritic cells are required for primary CD4+ T and B cell responses to soluble flagellin
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9:OCT
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Tidskriftsartikel (refereegranskat)abstract
- Systemic immunization with soluble flagellin (sFliC) from Salmonella Typhimurium induces mucosal responses, offering potential as an adjuvant platform for vaccines. Moreover, this engagement of mucosal immunity is necessary for optimal systemic immunity, demonstrating an interaction between these two semi-autonomous immune systems. Although TLR5 and CD103+CD11b+ cDC2 contribute to this process, the relationship between these is unclear in the early activation of CD4+ T cells and the development of antigen-specific B cell responses. In this work, we use TLR5-deficient mice and CD11c-cre.Irf4fl/fl mice (which have reduced numbers of cDC2, particularly intestinal CD103+CD11b+ cDCs), to address these points by studying the responses concurrently in the spleen and the mesenteric lymph nodes (MLN). We show that CD103+CD11b+ cDC2 respond rapidly and accumulate in the MLN after immunization with sFliC in a TLR5-dependent manner. Furthermore, we identify that whilst CD103+CD11b+ cDC2 are essential for the induction of primary T and B cell responses in the mucosa, they do not play such a central role for the induction of these responses in the spleen. Additionally, we show the involvement of CD103+CD11b+ cDC2 in the induction of Th2-associated responses. CD11c-cre.Irf4fl/fl mice showed a reduced primary FliC-specific Th2-associated IgG1 responses, but enhanced Th1-associated IgG2c responses. These data expand our current understanding of the mucosal immune responses promoted by sFliC and highlights the potential of this adjuvant for vaccine usage by taking advantage of the functionality of mucosal CD103+CD11b+ cDC2.
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| 3. |
- Kis, Loránd L., et al.
(författare)
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The STAT6 signaling pathway activated by the cytokines IL-4 and IL-13 induces expression of the Epstein-Barr virus-encoded protein LMP-1 in absence of EBNA-2 : implications for the type II EBV latent gene expression in Hodgkin lymphoma
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 117:1, s. 165-174
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Tidskriftsartikel (refereegranskat)abstract
- In line with the B-lymphotropic nature of EBV, the virus is present in several types of B cell lymphomas. EBV expresses a different set of latent genes in the associated tumors, such as EBNA-1 and LMPs (type II latency) in the classical Hodgkin lymphomas (cHL). We have previously reported that exposure of the in vitro EBV-converted, HL-derived cell line KMH2-EBV to CD40-ligand and IL-4 induced the expression of LMP-1. Here we show that exposure to IL-4 or IL-13 alone induced LMP-1 in the absence of EBNA-2. The induction of LMP-1 by IL-4 and IL-13 was mediated by the signal transducer STAT6 and a newly defined high-affinity STAT6-binding site in the LMP-1 promoter. IL-4 induced LMP-1 also in Burkitt lymphoma-derived lines and in tonsillar B cells infected with the EBNA-2-deficient EBV strain P3HR-1. Furthermore, co-culture of EBV-carrying BL cells with activated CD4(+) T cells resulted in the induction of LMP-1 in the absence of EBNA-2. As the Hodgkin/Reed-Sternberg are known to secrete IL-13, to have constitutively activated STAT6, and to be closely surrounded by CD4+ T cells, these mechanisms may be involved in the expression of LMP-1 in the EBV-positive cHLs.
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| 4. |
- Luda, Katarzyna M., et al.
(författare)
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IRF8 Transcription-Factor-Dependent Classical Dendritic Cells Are Essential for Intestinal T Cell Homeostasis
- 2016
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Ingår i: Immunity. - : Elsevier BV. - 1074-7613. ; 44:4, s. 860-874
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Tidskriftsartikel (refereegranskat)abstract
- The role of dendritic cells (DCs) in intestinal immune homeostasis remains incompletely defined. Here we show that mice lacking IRF8 transcription-factor-dependent DCs had reduced numbers of T cells in the small intestine (SI), but not large intestine (LI), including an almost complete absence of SI CD8αβ+ and CD4+CD8αα+ T cells; the latter requiring β8 integrin expression by migratory IRF8 dependent CD103+CD11b- DCs. SI homing receptor induction was impaired during T cell priming in mesenteric lymph nodes (MLN), which correlated with a reduction in aldehyde dehydrogenase activity by SI-derived MLN DCs, and inefficient T cell localization to the SI. These mice also lacked intestinal T helper 1 (Th1) cells, and failed to support Th1 cell differentiation in MLN and mount Th1 cell responses to Trichuris muris infection. Collectively these results highlight multiple non-redundant roles for IRF8 dependent DCs in the maintenance of intestinal T cell homeostasis.
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| 5. |
- Persson, Emma, et al.
(författare)
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Domainoid : domain-oriented orthology inference
- 2019
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Ingår i: BMC Bioinformatics. - : Springer Science and Business Media LLC. - 1471-2105. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Orthology inference is normally based on full-length protein sequences. However, most proteins contain independently folding and recurring regions, domains. The domain architecture of a protein is vital for its function, and recombination events mean individual domains can have different evolutionary histories. It has previously been shown that orthologous proteins may differ in domain architecture, creating challenges for orthology inference methods operating on full-length sequences. We have developed Domainoid, a new tool aiming to overcome these challenges faced by full-length orthology methods by inferring orthology on the domain level. It employs the InParanoid algorithm on single domains separately, to infer groups of orthologous domains.Results: This domain-oriented approach allows detection of discordant domain orthologs, cases where different domains on the same protein have different evolutionary histories. In addition to domain level analysis, protein level orthology based on the fraction of domains that are orthologous can be inferred. Domainoid orthology assignments were compared to those yielded by the conventional full-length approach InParanoid, and were validated in a standard benchmark.Conclusions: Our results show that domain-based orthology inference can reveal many orthologous relationships that are not found by full-length sequence approaches.
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| 6. |
- Persson, Magnus, et al.
(författare)
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Exploring the interplay between within-stand variation and thinning practices in southern Sweden
- 2024
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Ingår i: Forest Ecology and Management. - : Elsevier. - 0378-1127 .- 1872-7042. ; 561
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Tidskriftsartikel (refereegranskat)abstract
- The state of within-stand variation (WSV) in boreal, coniferous production forests and how it is dealt with in thinning operations is a scarcely researched topic. In the autumn of 2018, we surveyed a series of Norway spruce (Picea abies (L.) Karst) or Scots pine (Pinus sylvestris L.) dominated production stands scheduled for first commercial thinning from below. Here, we evaluate the potential causes of WSV in basal area, how WSV was addressed in the thinning operations, and finally how the stands and subsequent thinning practice conformed with the basal area target specified in the thinning guidelines. WSV in the yield attributes was defined as the dispersion in a stand attribute within a stand and quantified using the Qn scale estimator (a robust measure of dispersion). First, WSV in basal area at the time of first thinning was evaluated as a function of WSV in stem number and WSV in site index. Next, yield attributes before and after thinning were compared using paired ttests, and the future development of WSV in basal area was evaluated using linear mixed-effects models. Finally, the thinning practice was evaluated before and after thinning by modelling the compliance with the basal area target as a function of stem number and dominant height, also using linear mixed-effects models. WSV in basal area appeared to be influenced by WSV in site index and WSV in stem number for Norway spruce, but not for Scots pine. Thinning reduced the WSV in basal area, standing volume, and stem number, while dominant height, quadratic mean diameter and basal area weighted mean height remained unaffected. At first thinning, compliance with the thinning guideline increased with increasing stem density and dominant height. However, moderate to high compliance with the basal area target in the thinning guidelines was only reached for plots with elevated dominant height (>15 m) in combination with high stem number (>2250 N ha-1). Thus, the recommended range in dominant height (12-14 m) for first thinning was generally exceeded, which may be attributed to the generally low stem number at the time of thinning. This study suggests that sub-optimal regeneration efforts and management of young forests can lead to WSV across a wide range of stand attributes, and likely also reductions in yield. Thinning decreased WSV in basal area, standing volume and stem number, however, the plots were heavily thinned to such a degree that it could potentially cause production losses.
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| 7. |
- Ulvskog, Emma, 1975-, et al.
(författare)
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Oncological therapy to Swedish men with metastatic penile cancer 2000-2015
- 2021
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:1, s. 42-49
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Penile cancer is an uncommon disease with poor prognosis when spread to more than one inguinal lymph node. Recommendations on chemo- and radiotherapy in treatment guidelines are based on low-grade evidence. There are to our knowledge no described population-based cohort with detailed information on given oncological treatment and survival data. The aim of this study is to investigate in detail how men with metastatic penile cancer have been treated with chemotherapy and radiotherapy over time, and how survival varies with N-stage and given treatment.MATERIAL AND METHODS: For this observational cohort study all men in Sweden diagnosed with penile cancer with lymph node- or distant metastases 2000-2015 were identified through the Swedish National Penile Cancer Register (NPECR). Medical records were retrieved and 325 men were confirmed to have metastatic penile cancer (T-any, c or pN1-3 and/or M1). Information on treatments was collected. Causes of death were retrieved from the National Cause of Death Register (CDR).RESULTS: Chemotherapy and/or radiotherapy were given to 172 (53%) of all men. The use of oncological treatments with curative intent increased significantly during the study period, from 30% of men with c/pN2-3 diagnosed 2000-2003 compared with 57% of men diagnosed 2012-2015. Ninety-three (29%) men received oncological treatments with curative intent of whom 85/93 (91%) had stage c/pN2-3M0. Survival decreased with higher N-stage, M1-stage, and absence of oncological treatment with curative intent. For men with c/pN3-stage, the engagement of pelvic lymph nodes was entailed with lower survival than pN3 based on extra-nodal extension (ENE).CONCLUSION: The use of oncological treatment was below recommendations in guidelines but increased during the study period. Treatment was given predominantly to men with c/pN2-3 and M1-disease. Survival was higher among men treated with curative intent; this could be due to patient selection bias.
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