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Sökning: WFRF:(Sundström Görel) > Övrigt vetenskapligt/konstnärligt

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1.
  • Fällmar, Helena, 1980-, et al. (författare)
  • Neuropeptide Y/peptide YY receptor Y2 duplicate in zebrafish with unique introns displays distinct peptide binding properties
  • 2011
  • Ingår i: Comparative Biochemistry and Physiology - Part B. - : Elsevier BV. - 1096-4959 .- 1879-1107. ; 160:4, s. 166-173
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The neuropeptide Y-family peptides and receptors are involved in a broad range of functions including appetite regulation. Both the peptide genes and the receptor genes are known to have duplicated in early vertebrate evolution. The ancestral jawed vertebrate had 7 NPY receptors but the number varies between 4 and 7 in extant vertebrates. Herein we describe the identification of an additional NPY receptor in two fish species, zebrafish and medaka. They cluster together with the Y2 receptors in phylogenetic analyses and seem to be orthologous to each other that is why we have named them Y2-2. Their genes differ from Y2 in having introns in the coding region. Binding studies with zebrafish Y2-2 receptors show that the three endogenous peptides NPY, PYYa and PYYb have similar affinities, 0.15-0.66nM. This is in contrast to the Y2 receptor where they differed considerably from one another. N-terminally truncated NPY binds poorly and the Y2 antagonist BIIE0246 binds well to Y2-2, results that are reversed in comparison to Y2. Zebrafish Y2-2 mRNA was detected by PCR in the intestine and the eye, but not in the brain. In conclusion, we have found a novel Y2-like NPY/PYY receptor that probably arose in early teleost fish evolution.
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  • Larhammar, Dan, et al. (författare)
  • Evolution of vertebrate neuropeptide receptors
  • 2010
  • Ingår i: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 164:1, s. 20-20
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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5.
  • Sundström, Görel, 1977- (författare)
  • Evolution of the Neuropeptide Y and Opioid Systems and their Genomic Regions
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Two whole genome duplications (2R) occurred early in vertebrate evolution. By using combined information from phylogenetic analyses and chromosomal location of genes, this thesis delineates the evolutionary history of two receptor-ligand systems that expanded by these large scale events. A third whole genome duplication (3R) took place in the teleost fish lineage and has also contributed to the complexity of the gene families. New members of neuropeptide Y (NPY) peptide and receptor families were generated in 2R and 3R. Evolutionary comparisons show that the ancestral teleost fish had four peptides; subsequently, differential losses of the peptide genes occurred. In zebrafish the peptides and receptors display differences in tissue distribution and have  evolved binding preferences. In the frog Silurana tropicalis three peptides and six receptors werev identified, also displaying some differences in tissue distribution and receptor-ligand preferences. The findings in these experimental animals highlight both evolutionary conservation and lineage-specific features of the NPY system. The opioid system consists of four receptors and several peptides originating from four precursors. These results show that the receptor family was formed in 2R and 3R and that 2R together with one local duplication gave rise to the peptide family. The ancestral receptor and peptide genes were located on the same chromosome, suggesting coevolution. The Hox gene clusters, important in early development, provided the first strong evidence for 2R. Several neighboring gene families were analyzed and found to have expanded in 2R and 3R. In depth analyses of insulin-like growth factor binding protein (IGFBP) and voltage-gated sodium channel (SCN) gene families illustrates the importance of local duplications in combination with whole genome duplications in the formation of gene families. These findings provide additional strong evidence for two genome duplications in early vertebrate evolution and show that these events generated many new genes that could evolve new or more specialized functions.
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6.
  • Sundström, Görel, et al. (författare)
  • Phylogenetic and chromosomal analyses of multiple gene families syntenic with vertebrate Hox clusters
  • 2008
  • Ingår i: BMC Evolutionary Biology. - : Springer Science and Business Media LLC. - 1471-2148. ; 8, s. 254-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • BackgroundEver since the theory about two rounds of genome duplication (2R) in the vertebrate lineage was proposed, the Hox gene clusters have served as the prime example of quadruplicate paralogy in mammalian genomes. In teleost fishes, the observation of additional Hox clusters absent in other vertebrate lineages suggested a third tetraploidization (3R). Because the Hox clusters occupy a quite limited part of each chromosome, and are special in having position-dependent regulation within the multi-gene cluster, studies of syntenic gene families are needed to determine the extent of the duplicated chromosome segments. We have analyzed in detail 14 gene families that are syntenic with the Hox clusters to see if their phylogenies are compatible with the Hox duplications and the 2R/3R scenario. Our starting point was the gene family for the NPY family of peptides located near the Hox clusters in the pufferfish Takifugu rubripes, the zebrafish Danio rerio, and human.ResultsSeven of the gene families have members on at least three of the human Hox chromosomes and two families are present on all four. Using both neighbor-joining and quartet-puzzling maximum likelihood methods we found that 13 families have a phylogeny that supports duplications coinciding with the Hox cluster duplications. One additional family also has a topology consistent with 2R but due to lack of urochordate or cephalocordate sequences the time window when these duplications could have occurred is wider. All but two gene families also show teleost-specific duplicates.ConclusionBased on this analysis we conclude that the Hox cluster duplications involved a large number of adjacent gene families, supporting expansion of these families in the 2R, as well as in the teleost 3R tetraploidization. The gene duplicates presumably provided raw material in early vertebrate evolution for neofunctionalization and subfunctionalization.
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  • Torabi Moghadam, Behrooz, et al. (författare)
  • An unsupervised approach subgroups cancer types by distinct local DNA methylation patterns
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Cancer is one of the most common causes of death in humans. It can arise from many different cell types, and even cancers originating from the same tissue can constitute a heterogeneous group of diseases. While cytogenetics, the analysis of mutations and karyotypic alterations, has greatly improved the accuracy of diagnosis, it is likely that there are more categories in which cancers can be divided than is known today. Moreover, new biomarkers confirming existing classification schemes are desirable. Here, we interrogated the DNA methylation (DNAm) landscape as a novel indicator for discerning cancer subtypes.We developed and applied an unsupervised method, methylSaguaro, which is based on the combination of a Hidden Markov Model and a Neural Net. We first compared the concept of hypothesizing patterns and grouping to statistical methods that require a priori hypotheses to perform enrichment tests. We then analyzed samples from four cancer groups, Gliomas, Chronic Lymphocytic Leukemia (CLL), Renal Cell Carcinomas (RCC), and Acute Myeloid Leukemia (AML). On gliomas and CLL, we confirmed known cancer groupings in DNAm that perfectly correspond to known mutations. On Renal Cell Carcinomas, our method disagrees with the histological classification on 4% of the samples, and finds a novel cluster, suggesting that there might be a novel subtype that was hitherto unknown. On AML, methylSaguaro spreads the samples out on a continuous spectrum, enriching one end with patients assessed as having “poor” risk based on cytogenetics, but indicating that DNAm patterns would suggest a different risk assessment. Since methylSaguaro reports both the patterns and the specific sites behind the signals, we analyzed regions and genes indicative of subtypes across the cancers, revealing 41 genes affected by alterations in more than one cancer. In summary, we expect that DNAm, coupled with a hypothesis-free analysis method, will add to the set of clinical instruments to diagnose, assess, and treat cancer.
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9.
  • Xu, Bo, 1980-, et al. (författare)
  • Neuropeptide Y family receptors Y1 and Y2 from sea lamprey, Petromyzon marinus: cloning and pharmacological characterization
  • 2015
  • Ingår i: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 222, s. 106-115
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The vertebrate gene family for neuropeptide Y (NPY) receptors expanded by duplication of the chromosome carrying the ancestral Y1–Y2–Y5 gene triplet. After loss of some duplicates, the ancestral jawed vertebrate had seven receptor subtypes forming the Y1 (including Y1, Y4, Y6, Y8), Y2 (including Y2, Y7) and Y5 (only Y5) subfamilies. Lampreys are considered to have experienced the same chromosome duplications as gnathostomes and should also be expected to have multiple receptor genes. However, previously only a Y4-like and a Y5 receptor have been cloned and characterized. Here we report the cloning and characterization of two additional receptors from the sea lamprey Petromyzon marinus. Sequence phylogeny alone could not with certainty assign their identity, but based on synteny comparisons of P. marinus and the Arctic lamprey, Lethenteron camtschaticum, with jawed vertebrates, the two receptors most likely are Y1 and Y2. Both receptors were expressed in human HEK293 cells and inositol phosphate assays were performed to determine the response to the three native lamprey peptides NPY, PYY and PMY. The three peptides have similar potencies in the nanomolar range for Y1. No obvious response to the three peptides was detected for Y2. Synteny analysis supports identification of the previously cloned receptor as Y4. No additional NPY receptor genes could be identified in the presently available lamprey genome assemblies. Thus, four NPY-family receptors have been identified in lampreys, orthologs of the same subtypes as in humans (Y1, Y2, Y4 and Y5), whereas many other vertebrate lineages have retained additional ancestral subtypes.
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