| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Greenhalgh, Christopher J, et al.
(författare)
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SOCS2 negatively regulates growth hormone action in vitro and in vivo.
- 2005
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Ingår i: The Journal of clinical investigation. - 0021-9738. ; 115:2, s. 397-406
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Tidskriftsartikel (refereegranskat)abstract
- Mice deficient in SOCS2 display an excessive growth phenotype characterized by a 30-50% increase in mature body size. Here we show that the SOCS2-/- phenotype is dependent upon the presence of endogenous growth hormone (GH) and that treatment with exogenous GH induced excessive growth in mice lacking both endogenous GH and SOCS2. This was reflected in terms of overall body weight, body and bone lengths, and the weight of internal organs and tissues. A heightened response to GH was also measured by examining GH-responsive genes expressed in the liver after exogenous GH administration. To further understand the link between SOCS2 and the GH-signaling cascade, we investigated the nature of these interactions using structure/function and biochemical interaction studies. Analysis of the 3 structural motifs of the SOCS2 molecule revealed that each plays a crucial role in SOCS2 function, with the conserved SOCS-box motif being essential for all inhibitory function. SOCS2 was found to bind 2 phosphorylated tyrosines on the GH receptor, and mutational analysis of these amino acids showed that both were essential for SOCS2 function. Together, the data provide clear evidence that SOCS2 is a negative regulator of GH signaling.
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| 4. |
- Gray, Howard W. I., et al.
(författare)
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Comparative biogeography and the evolution of population structure for bottlenose and common dolphins in the Indian Ocean
- 2021
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Ingår i: Journal of Biogeography. - : Wiley. - 0305-0270 .- 1365-2699. ; 48:7, s. 1654-1668
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Tidskriftsartikel (refereegranskat)abstract
- Aim: In the marine environment, where there are few physical boundaries to gene flow, there is often nevertheless intraspecific diversity with consequences for effective conservation and management. Here, we compare two closely related dolphin species with a shared distribution in the Indian Ocean (IO) to better understand the biogeographic drivers of their population structure.Location: Global oceans and seas with a focus on the Indian OceanTaxon: Tursiops sp. and Delphinus sp.Methods: Bayesian, ordination, assignment, statistical and phylogenetic analyses to assess phylogeography, connectivity and population structure using microsatellite and mitochondrial DNA genetic markers.Results: Both Tursiops sp. and Delphinus sp. showed population structure across the western IO and, in each case, populations in the Arabian Sea (off India, Pakistan and Oman) were most differentiated. Comparisons with other populations worldwide revealed independent lineages in this geographic region for both genera. For T. aduncus, (for which multiple sites within the IO could be compared), Bayesian modelling best supported a scenario of expansion southwards following a bottleneck event resulting in differentiation between the northern and western IO. For Delphinus, the same pattern is even more pronounced. Populations in the Arabian Sea region of the north-western IO show genetic isolation for each of the two genera, consistent with other studies of cetacean species in this region.Main conclusions: We propose that changes in the intensity of the southwest monsoon during the climate cycles of the Pleistocene could have affected regional patterns of productivity and represent an important biogeographic driver promoting the observed patterns of differentiation and population dynamics seen in our focal species. Patterns of population genetic structure are consistent with phenotypic differences, suggesting an influence from distinct habitats and resources, and emphasising the need for effective conservation measures in this geographic region.
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| 5. |
- Wood, Laura D, et al.
(författare)
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The genomic landscapes of human breast and colorectal cancers.
- 2007
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 318:5853, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.
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