| 1. |
|
|
| 2. |
- Ali, Mina, et al.
(författare)
-
The multiple myeloma risk allele at 5q15 lowers ELL2 expression and increases ribosomal gene expression
- 2018
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 1649-
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, we identified ELL2 as a susceptibility gene for multiple myeloma (MM). To understand its mechanism of action, we performed expression quantitative trait locus analysis in CD138+ plasma cells from 1630 MM patients from four populations. We show that the MM risk allele lowers ELL2 expression in these cells (Pcombined = 2.5 × 10−27; βcombined = −0.24 SD), but not in peripheral blood or other tissues. Consistent with this, several variants representing the MM risk allele map to regulatory genomic regions, and three yield reduced transcriptional activity in plasmocytoma cell lines. One of these (rs3777189-C) co-locates with the best-supported lead variants for ELL2 expression and MM risk, and reduces binding of MAFF/G/K family transcription factors. Moreover, further analysis reveals that the MM risk allele associates with upregulation of gene sets related to ribosome biogenesis, and knockout/knockdown and rescue experiments in plasmocytoma cell lines support a cause–effect relationship. Our results provide mechanistic insight into MM predisposition.
|
|
| 3. |
- Allard, Anna, et al.
(författare)
-
INSTRUKTION FÖR BILDTOLKNINGSARBETET VID NATIONELL INVENTERING AV LANDSKAPET I SVERIGE NILS ÅR 2003
- 2003
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Denna manual är utarbetad för att användas vid flygbildstolkningsarbetet inom det nationella miljöövervakningsprogrammet Nationell Inventering av Landskapet i Sverige (NILS). NILS är en del av Naturvårdsverkets nationella miljöövervakning och omfattar alla landmiljöer – jordbruksmark, våtmark, bebyggd miljö, skogmark, kust och fjäll. Operativt drivs programmet av Sveriges lantbruksuniversitet, Institutionen för skoglig resurshushållning och geomatik i Umeå. Manualen är framtagen som en del i metodutvecklingsarbetet med NILS. Förutom författarna till manualen har ett stort antal personer bidragit med synpunkter och delar av texten. Ett stort tack till Per-Anders Esseen, Anders Glimskär, Mats Högström, Per Löfgren, Ronny Löfstrand och Anki Weibull från Sveriges Lantbruksuniversitet samt Margareta Ihse Stockholms Universitet, Ola Inghe Naturvårdsverket, Anneli Mattisson Länsstyrelsen i Stockholm och Sture Westerberg Länsstyrelsen i Norrbotten. Manualen inleds med en beskrivning av NILS-programmet och en översiktlig beskrivning hur inventeringen är uppbyggd. Därefter följer en mer detaljerad beskrivning av flygbildstolkningsarbetet. I slutet av manualen finns tolkningsinstruktioner och definitioner på olika begrepp som används i tolkningsarbetet.
|
|
| 4. |
|
|
| 5. |
- Allard, Anna, et al.
(författare)
-
Manual for Aerial Photo Interpretation in the National Inventory of Landscapes in Sweden : NILS
- 2003
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This manual is developed for the aerial photo interpretation work within the Swedish monitoring programme National Inventory of Landscapes in Sweden (NILS).NILS is a part of the national environmental monitoring activities of the Swedish Environmental Protection Agency (EPA) and includes all terrestrial environments – agricultural lands, wetlands, urban environments, forests, and coastal and alpine areas. Operationally, the programme is conducted by the Swedish University of Agricultural Sciences, Department of Forest Resource Management and Geomatics in Umeå.The manual is prepared as part of the methodology development work within NILS. In addition to the authors, some external reviewers have given their comments on the text and also contributed with material. Special thanks to Per-Anders Esseen, Anders Glimskär, Mats Högström, Per Löfgren, Ronny Löfstrand, Anki Weibull (all from the Swedish University of Agricultural Sciences), Margareta Ihse (Stockholm University) Ola Inghe (Swedish Environmental Protection Agency), Anneli Mattisson (County of Stockholm), and Sture Westerberg (County of Norrbotten). We would also like to thank Ylva melin and Heather Reese for the translation work to the English language.Following this introduction, the manual describes the NILS programme and outlines the structure of the inventory. This is followed by a detailed description of how the aerial photo interpretation is performed. Finally, instructions and definitions for the interpretation work are given. Some of the figures are mad in Swedish, but explanatory texts are given to the figures.
|
|
| 6. |
- Elkabets, Moshe, et al.
(författare)
-
Human tumors instigate granulin-expressing hematopoietic cells that promote malignancy by activating stromal fibroblasts in mice
- 2011
-
Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 121:2, s. 784-799
-
Tidskriftsartikel (refereegranskat)abstract
- Systemic instigation is a process by which endocrine signals sent from certain tumors (instigators) stimulate BM cells (BMCs), which are mobilized into the circulation and subsequently foster the growth of otherwise indolent carcinoma cells (responders) residing at distant anatomical sites. The identity of the BMCs and their specific contribution or contributions to responder tumor growth have been elusive. Here, we have demonstrated that Scal(+)cKit(-) hematopoietic BMCs of mouse hosts bearing instigating tumors promote the growth of responding tumors that form with a myofibroblast-rich, desmoplastic stroma. Such stroma is almost always observed in malignant human adenocarcinomas and is an indicator of poor prognosis. We then identified granulin (GRN) as the most upregulated gene in instigating Scal(+)cKit(-) BMCs relative to counterpart control cells. The GRN(+) BMCs that were recruited to the responding tumors induced resident tissue fibroblasts to express genes that promoted malignant tumor progression; indeed, treatment with recombinant GRN alone was sufficient to promote desmoplastic responding tumor growth. Further, analysis of tumor tissues from a cohort of breast cancer patients revealed that high GRN expression correlated with the most aggressive triple-negative, basal-like tumor subtype and reduced patient survival. Our data suggest that GRN and the unique hematopoietic BMCs that produce it might serve as novel therapeutic targets.
|
|
| 7. |
- Jonsson, Stefan, et al.
(författare)
-
Identification of sequence variants influencing immunoglobulin levels
- 2017
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 49:8, s. 1182-1191
-
Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 × 10(-55), β = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 × 10(-8), β = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.
|
|
| 8. |
- Lechman, Eric R, et al.
(författare)
-
miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells.
- 2016
-
Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 29:2, s. 214-228
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance.
|
|
| 9. |
- Mitchell, Jonathan S., et al.
(författare)
-
Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P = 1.31 x 10(-8)), 6q21 (rs9372120, P = 9.09 x 10(-15)), 7q36.1 (rs7781265, P = 9.71 x 10(-9)), 8q24.21 (rs1948915, P = 4.20 x 10(-11)), 9p21.3 (rs2811710, P = 1.72 x 10(-13)), 10p12.1 (rs2790457, P = 1.77 x 10(-8)), 16q23.1 (rs7193541, P = 5.00 x 10(-12)) and 20q13.13 (rs6066835, P = 1.36 x 10(-13)), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
|
|
| 10. |
|
|
