| 1. |
- Tanskanen, T., et al.
(author)
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Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci
- 2018
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In: International Journal of Cancer. - Stockholm : Wiley. - 0020-7136 .- 1097-0215. ; 142:3, s. 540-546
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Journal article (peer-reviewed)abstract
- Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p=2.08 x 10(-4); OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p=1.50 x 10(-9); OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate<0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.
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| 2. |
- Guerova, G., et al.
(author)
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National Status Reports
- 2020
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In: Advanced GNSS Tropospheric Products for Monitoring Severe Weather Events and Climate. - Cham : Springer International Publishing. - 9783030139001 ; , s. 403-481
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Book chapter (other academic/artistic)abstract
- In this section a summary of the national progress reports is given. GNSS4SWEC Management Committee (MC) members provided outline of the work conducted in their countries combining input from different partners involved. In the COST Action paticipated member from 32 COST countries, 1 Near Neighbour Country and 8 Intrantional Partners from Australia, Canada, Hong Kong and USA. The text reflects the state as of 1 January 2018.
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| 3. |
- Adhikari, Subash, et al.
(author)
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A high-stringency blueprint of the human proteome
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Research review (peer-reviewed)abstract
- The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.
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| 4. |
- Zhao, Ziran, et al.
(author)
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PPP2R2A prostate cancer haploinsufficiency is associated with worse prognosis and a high vulnerability to B55 alpha/PP2A reconstitution that triggers centrosome destabilization
- 2019
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In: Oncogenesis. - : NATURE PUBLISHING GROUP. - 2157-9024. ; 8
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Journal article (peer-reviewed)abstract
- The PPP2R2A gene encodes the B55 alpha regulatory subunit of PP2A. Here, we report that PPP2R2A is hemizygously lost in similar to 42% of prostate adenocarcinomas, correlating with reduced expression, poorer prognosis, and an increased incidence of hemizygous loss (>75%) in metastatic disease. Of note, PPP2R2A homozygous loss is less common (5%) and not increased at later tumor stages. Reduced expression of B55 alpha is also seen in prostate tumor tissue and cell lines. Consistent with the possibility that complete loss of PPP2R2A is detrimental in prostate tumors, PPP2R2A deletion in cells with reduced but present B55 alpha reduces cell proliferation by slowing progression through the cell cycle. Remarkably, B55 alpha-low cells also appear addicted to lower B55 alpha expression, as even moderate increases in B55 alpha expression are toxic. Reconstitution of B55 alpha expression in prostate cancer (PCa) cell lines with low B55 alpha expression reduces proliferation, inhibits transformation and blocks xenograft tumorigenicity. Mechanistically, we show B55 alpha reconstitution reduces phosphorylation of proteins essential for centrosomal maintenance, and induces centrosome collapse and chromosome segregation failure; a first reported link between B55 alpha/PP2A and the vertebrate centrosome. These effects are dependent on a prolonged metaphase/anaphase checkpoint and are lethal to PCa cells addicted to low levels of B55 alpha. Thus, we propose the reduction in B55 alpha levels associated with hemizygous loss is necessary for centrosomal integrity in PCa cells, leading to selective lethality of B55 alpha reconstitution. Such a vulnerability could be targeted therapeutically in the large pool of patients with hemizygous PPP2R2A deletions, using pharmacologic approaches that enhance PP2A/B55 alpha activity.
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- Fagerberg, Linn, et al.
(author)
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Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics
- 2014
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In: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 13:2, s. 397-406
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Journal article (peer-reviewed)abstract
- Global classification of the human proteins with regards to spatial expression patterns across organs and tissues is important for studies of human biology and disease. Here, we used a quantitative transcriptomics analysis (RNA-Seq) to classify the tissue-specific expression of genes across a representative set of all major human organs and tissues and combined this analysis with antibody- based profiling of the same tissues. To present the data, we launch a new version of the Human Protein Atlas that integrates RNA and protein expression data corresponding to 80% of the human protein-coding genes with access to the primary data for both the RNA and the protein analysis on an individual gene level. We present a classification of all human protein-coding genes with regards to tissue-specificity and spatial expression pattern. The integrative human expression map can be used as a starting point to explore the molecular constituents of the human body.
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- Omenn, Gilbert S., et al.
(author)
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Research on the Human Proteome Reaches a Major Milestone : > 90% of Predicted Human Proteins Now Credibly Detected, According to the HUPO Human Proteome Project
- 2020
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 19:12, s. 4735-4746
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Journal article (peer-reviewed)abstract
- According to the 2020 Metrics of the HUPO Human Proteome Project (HPP), expression has now been detected at the protein level for >90% of the 19 773 predicted proteins coded in the human genome. The HPP annually reports on progress made throughout the world toward credibly identifying and characterizing the complete human protein parts list and promoting proteomics as an integral part of multiomics studies in medicine and the life sciences. NeXtProt release 2020-01 classified 17 874 proteins as PE1, having strong protein-level evidence, up 180 from 17 694 one year earlier. These represent 90.4% of the 19 773 predicted coding genes (all PE1,2,3,4 proteins in neXtProt). Conversely, the number of neXtProt PE2,3,4 proteins, termed the "missing proteins" (MPs), was reduced by 230 from 2129 to 1899 since the neXtProt 2019-01 release. PeptideAtlas is the primary source of uniform reanalysis of raw mass spectrometry data for neXtProt, supplemented this year with extensive data from MassIVE. PeptideAtlas 2020-01 added 362 canonical proteins between 2019 and 2020 and MassIVE contributed 84 more, many of which converted PE1 entries based on non-MS evidence to the MS-based subgroup. The 19 Biology and Disease-driven B/D-HPP teams continue to pursue the identification of driver proteins that underlie disease states, the characterization of regulatory mechanisms controlling the functions of these proteins, their proteoforms, and their interactions, and the progression of transitions from correlation to coexpression to causal networks after system perturbations. And the Human Protein Atlas published Blood, Brain, and Metabolic Atlases.
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- Akeus, Paulina, et al.
(author)
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Regulatory T cells reduce endothelial neutral sphingomyelinase 2 to prevent T-cell migration into tumors
- 2021
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In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 51:9, s. 2317-2329
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Journal article (peer-reviewed)abstract
- Endothelial cells are key regulators of transendothelial migration and their secretion of chemokines and expression of adhesion molecules facilitates lymphocyte entry into tissues. Previously, we demonstrated that Tregs can reduce transendothelial migration of T cells into tumors by decreasing endothelial CXCL10 secretion, but the mechanism by which this occurs is still not known. In this study, we aimed to define how Tregs decrease transendothelial migration into tumors. mRNA sequencing of intestinal tumor endothelial cells from Treg depleted mice identified neutral sphingomyelinase 2 (nSMase2) as a gene downregulated in the presence of Tregs. nSMase2 is expressed in human umbilical vein endothelial cells (HUVECs) and was decreased after coculture with Tregs. Furthermore, blocking of nSMase2 activity in vitro decreased VCAM1, CX3CL1, and CXCL10 expression in HUVECs, mirroring the same decrease found in Treg cocultures. In the APC(min/+) mouse model of intestinal cancer, nSMase2 is lower in tumor endothelial cells than in unaffected small intestine and chronic treatment with a nSMase2 inhibitor suppressed the increased migration that is otherwise seen in the absence of Tregs. We conclude that nSMase2 is an important mediator in endothelial cells supporting transendothelial migration, which may be targeted by Tregs to reduce T-cell migration into tumors.
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| 13. |
- Al Hashmi, S., et al.
(author)
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Omega-3 from fish oil augments GVHD through the enhancement of chemotherapy conditioning regimen and selective FoxP3 depletion
- 2013
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In: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 48:6, s. 843-848
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Journal article (peer-reviewed)abstract
- Omega-3 is known to enhance the effects of several chemotherapeutic agents and to exert several immunoregulatory actions In the present study, we evaluated the effects of a 21-day feeding regimen with omega-3-rich fish oil (FO) and its corresponding control, omega-6 rich corn oil (CO), on the BU-CY conditioning and the development of GVHD after BMT in mice. Before conditioning, FO, but not CO, feeding caused a significant attenuation in the number and functionality of splenic FoxP3+ T regulatory cells (Treg). FO feeding also enhanced the effects of the conditioning through severe depletion of Treg cells in the spleen and CD11b+ myeloid cells in both the BM and spleen. Consequently, FO-fed animals conditioned with BU-CY showed exacerbated GVHD following transplantation with allogeneic BM and splenic cells. In contrast, identical transplantation in CO-fed mice resulted in poor engraftment and body weight loss. Moreover, in standard-fed recipients, BMT with cells from FO-fed donors resulted in moderate GVHD and improved the survival time, whereas BMT with cells from CO-fed donors shortened the survival time and caused anemia. We conclude that food supplements should be considered in patients undergoing BMT and/or chemotherapy treatment.
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| 31. |
- Carreras-Puigvert, Jordi, et al.
(author)
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A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family
- 2017
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 8:1
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Journal article (peer-reviewed)abstract
- The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes. To a certain extent, their substrate preference redundancies correlate with structural classes, thus linking structure and activity relationships. To elucidate interdependence among the NUDIX hydrolases, we pairwise deplete them generating an epistatic interaction map, evaluate cell cycle perturbations upon knockdown in normal and cancer cells, and analyse their protein and mRNA expression in normal and cancer tissues. Using a novel FUSION algorithm, we integrate all data creating a comprehensive NUDIX enzyme profile map, which will prove fundamental to understanding their biological functionality.
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| 43. |
- Hofstedt, Annika, et al.
(author)
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Pilot data findings from the Gothenburg treatment for gaming disorder: a cognitive behavioral treatment manual
- 2023
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In: Frontiers in Psychiatry. - 1664-0640. ; 14
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Journal article (peer-reviewed)abstract
- Background: Gaming disorder (GD) is a new diagnosis included in the latest edition of the International Classification of Disease -11. Recently conducted international studies suggest a prevalence rate close to 2% for GD, highlighting the need for effective treatments for this patient population. Internationally there are few studies investigating effective treatments specifically designed for this condition. In this pilot study, we wanted to test a newly developed method, the Gothenburg Treatment for Gaming Disorder (GOT-TO-GO) manual; a 15-week cognitive behavioral therapy treatment for GD.Method: This study utilized a single group design with pretest, post-test and a three- and six-month follow-up, with measures of severity of GD and mood. The participants (n = 28) were treatment-seeking adults with GD, aged 17 to 49 years.Results: The results show a statistically significant decrease in symptoms of GD after treatment. Hours of gaming per week also decreased concomitantly with a 100% increase in non-gaming leisure hours. The decrease in symptoms of GD was maintained at the 3-months follow-up after treatment. Correspondingly we saw a decrease in both depression and anxiety that also was upheld 3 months after treatment.Conclusion: As GD is a new diagnostic concept more research is needed, also taking psychiatric comorbidity into consideration, to arrive at evidence-based conclusions regarding effective treatments. Considering the promising results in this small pilot study with large behavioral changes and reduced symptoms of GD, upheld at least 3 months after treatment, a larger randomized controlled study is warranted.
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| 47. |
- Larsson, Peter, 1966-, et al.
(author)
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Wireless communications system with detection of foreign radiation sources
- 2001
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Patent (pop. science, debate, etc.)abstract
- NOVELTY - Involves enabling one node in the system to function as a central node which can make measurements on a frequency in a frequency band used by the system. The measurements detect if a frequency is being used by a transmitter foreign to the system. USE - For use in a wireless communications system with several broadcasting nodes e.g. Wireless Local Area Network (WLAN). ADVANTAGE - Enables WLAN to detect if e.g. nearby radar system transmitter is using same frequency and to take necessary steps if so. DETAILED DESCRIPTION - The measurement is enabled by the central node transmitting a message to other nodes in the system. The message is predefined within the system as a message prohibiting all nodes from transmitting during a certain interval. DESCRIPTION OF DRAWING(S) - The drawing shows the signaling used when making measurements according to the method.
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| 49. |
- Lin, CH, et al.
(author)
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Human ex vivo spinal cord slice culture as a useful model of neural development, lesion, and allogeneic neural cell therapy
- 2020
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In: Stem cell research & therapy. - : Springer Science and Business Media LLC. - 1757-6512. ; 11:1, s. 320-
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Journal article (peer-reviewed)abstract
- BackgroundThere are multiple promising treatment strategies for central nervous system trauma and disease. However, to develop clinically potent and safe treatments, models of human-specific conditions are needed to complement in vitro and in vivo animal model-based studies.MethodsWe established human brain stem and spinal cord (cross- and longitudinal sections) organotypic cultures (hOCs) from first trimester tissues after informed consent by donor and ethical approval by the Regional Human Ethics Committee, Stockholm (lately referred to as Swedish Ethical Review Authority), and The National Board of Health and Welfare, Sweden. We evaluated the stability of hOCs with a semi-quantitative hOC score, immunohistochemistry, flow cytometry, Ca2+signaling, and electrophysiological analysis. We also applied experimental allogeneic human neural cell therapy after injury in the ex vivo spinal cord slices.ResultsThe spinal cord hOCs presented relatively stable features during 7–21 days in vitro (DIV) (except a slightly increased cell proliferation and activated glial response). After contusion injury performed at 7 DIV, a significant reduction of the hOC score, increase of the activated caspase-3+cell population, and activated microglial populations at 14 days postinjury compared to sham controls were observed. Such elevation in the activated caspase-3+population and activated microglial population was not observed after allogeneic human neural cell therapy.ConclusionsWe conclude that human spinal cord slice cultures have potential for future structural and functional studies of human spinal cord development, injury, and treatment strategies.
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