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- Maxwell, Christopher A., et al.
(författare)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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| 2. |
- Aronsson, Mora, et al.
(författare)
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Sveriges arter och naturtyper i EU:s art- och habitatdirektiv : Resultat från rapportering 2019 till EU av bevarandestatus 2013-2018
- 2020
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sverige har en variationsrik natur med storslagen fjällmiljö, myllrande våtmarker, vattendrag och sjöar, kust och hav, skogar och odlingslandskap, alla med ett rikt växt och djurliv. Den här fantastiska biologiska mångfalden tas ofta för given och ibland som en lyx, men oavsett vilket är det en förutsättning för vår överlevnad.2019 rapporterade Sverige statusen till EU för perioden 2013–2018 för de naturtyper och arter i Sverige som är listade i art- och habitatdirektivet. Den berättar att 20 procent av naturtyperna och 40 procent av arterna mår bra. Den biologiska mångfalden är hårt trängd i såväl Sverige som i andra EU-länder.Den här rapporten sammanfattar Sveriges rapportering och innehåller beskrivningar av status för naturtyper och arter, påverkan, hot och trender. Rapporten ger kunskap om tillståndet för den biologiska mångfalden i Sverige med hjälp av de arter och naturtyper som är listade i EU:s art- och habitatdirektiv.Rapporten visar hur naturmiljöerna i Sverige förändas, och sammanfattar den senaste kunskapen om vilka faktorer som driver dessa förändringar. Även exempel på hur vi genom restaurerings- och skötselåtgärder kan hejda förlusten av biologisk mångfald tas upp.
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| 3. |
- Kelpšas, Vinardas, et al.
(författare)
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Evolving escherichia coli host strains for efficient deuterium labeling of recombinant proteins using sodium pyruvate-d3
- 2021
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:18
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Tidskriftsartikel (refereegranskat)abstract
- Labeling of proteins with deuterium (2H) is often necessary for structural biology tech-niques, such as neutron crystallography, NMR spectroscopy, and small-angle neutron scattering. Perdeuteration in which all protium (1H) atoms are replaced by deuterium is a costly process. Typ-ically, expression hosts are grown in a defined medium with heavy water as the solvent, which is supplemented with a deuterated carbon source. Escherichia coli, which is the most widely used host for recombinant protein production, can utilize several compounds as a carbon source. Glycerol-d8 is often used as a carbon source for deuterium labelling due to its lower cost compered to glucose-d7 . In order to expand available options for recombinant protein deuteration, we investigated the possibility of producing a deuterated carbon source in-house. E. coli can utilize pyruvate as a carbon source and pyruvate-d3 can be made by a relatively simple procedure. To circumvent the very poor growth of E. coli in minimal media with pyruvate as sole carbon source, adaptive laboratory evolution for strain improvement was applied. E. coli strains with enhanced growth in minimal pyruvate medium was subjected to whole genome sequencing and the genetic changes were revealed. One of the evolved strains was adapted for the widely used T7 RNA polymerase overexpression systems. Using the improved strain E. coli DAP1(DE3) and in-house produced deuterated carbon source (pyru-vic acid-d4 and sodium pyruvate-d3 ), we produce deuterated (>90%) triose-phosphate isomerase, at quantities sufficient enough for large volume crystal production and subsequent analysis by neutron crystallography.
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