| 1. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 2. |
- Tchaplyguine, Maxim, et al.
(författare)
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Absolute core-level binding energy shifts between atom and solid: The Born-Haber cycle revisited for free nanoscale metal clusters
- 2008
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 166, s. 38-44
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Tidskriftsartikel (refereegranskat)abstract
- Core-level binding energy shifts between the free atom and corresponding large clusters, the latter closely approximating the infinite solid, have been experimentally derived for several elemental metals. The cluster core-level binding energies in question have been determined relative to the vacuum level using synchrotron-based photoelectron spectroscopy. As expected, the experimental shift values show reasonable agreement with those calculated using the thermochemical Born–Haber cycle approach. The largest uncertainty factors defining the discrepancies between the experiment and the model, such as the difference in the multiplet structure of free atoms and the solid, the in some cases indirectly established cluster work functions, and the metal solvation energy, are discussed.
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| 3. |
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| 4. |
- Abarenkov, Kessy, et al.
(författare)
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Annotating public fungal ITS sequences from the built environment according to the MIxS-Built Environment standard – a report from a May 23-24, 2016 workshop (Gothenburg, Sweden)
- 2016
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Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 16, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Recent molecular studies have identified substantial fungal diversity in indoor environments. Fungi and fungal particles have been linked to a range of potentially unwanted effects in the built environment, including asthma, decay of building materials, and food spoilage. The study of the built mycobiome is hampered by a number of constraints, one of which is the poor state of the metadata annotation of fungal DNA sequences from the built environment in public databases. In order to enable precise interrogation of such data – for example, “retrieve all fungal sequences recovered from bathrooms” – a workshop was organized at the University of Gothenburg (May 23-24, 2016) to annotate public fungal barcode (ITS) sequences according to the MIxS-Built Environment annotation standard (http://gensc.org/mixs/). The 36 participants assembled a total of 45,488 data points from the published literature, including the addition of 8,430 instances of countries of collection from a total of 83 countries, 5,801 instances of building types, and 3,876 instances of surface-air contaminants. The results were implemented in the UNITE database for molecular identification of fungi (http://unite.ut.ee) and were shared with other online resources. Data obtained from human/animal pathogenic fungi will furthermore be verified on culture based metadata for subsequent inclusion in the ISHAM-ITS database (http://its.mycologylab.org).
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| 5. |
- Adolphi, Florian, et al.
(författare)
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Persistent link between solar activity and Greenland climate during the Last Glacial Maximum
- 2014
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Ingår i: Nature Geoscience. - 1752-0908 .- 1752-0894. ; 7:9, s. 662-666
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Tidskriftsartikel (refereegranskat)abstract
- Changes in solar activity have previously been proposed to cause decadal- to millennial-scale fluctuations in both the modern and Holocene climates(1). Direct observational records of solar activity, such as sunspot numbers, exist for only the past few hundred years, so solar variability for earlier periods is typically reconstructed from measurements of cosmogenic radionuclides such as Be-10 and C-14 from ice cores and tree rings(2,3). Here we present a high-resolution Be-10 record from the ice core collected from central Greenland by the Greenland Ice Core Project (GRIP). The record spans from 22,500 to 10,000 years ago, and is based on new and compiled data(4-6). Using C-14 records(7,8) to control for climate-related influences on Be-10 deposition, we reconstruct centennial changes in solar activity. We find that during the Last Glacial Maximum, solar minima correlate with more negative delta O-18 values of ice and are accompanied by increased snow accumulation and sea-salt input over central Greenland. We suggest that solar minima could have induced changes in the stratosphere that favour the development of high-pressure blocking systems located to the south of Greenland, as has been found in observations and model simulations for recent climate(9,10). We conclude that the mechanism behind solar forcing of regional climate change may have been similar under both modern and Last Glacial Maximum climate conditions.
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| 6. |
- Ahmed, Aisha S, et al.
(författare)
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NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease.
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- The role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been highlighted in mechanisms underlying inflammatory and neuropathic pain processes. The present study was designed to investigate whether NF-κB signaling is associated with pain-related neuropeptide expression in patients with chronic back pain related to degenerative disc disease (DDD). Intervertebral disc (IVD) tissues were collected from forty DDD patients undergoing disc replacement or fusion surgery, and from eighteen postmortem (PM) control subjects. RELA, NFKB1, CGRP, TAC1, TRPV1, and MMP-3 gene expression were analyzed by RT-qPCR, while NF-κB subunit RelA and NF-κB1⁻DNA binding in nuclear extracts and calcitonin gene related peptide (CGRP), substance P (SP), and transient receptor potential, subfamily V, member 1 (TRPV1) protein levels in cytosolic extracts of tissues were assessed by enzyme-linked immunosorbent assay (ELISA). An upregulated NF-κB1⁻DNA binding, and higher CGRP and TRPV1 protein levels were observed in DDD patients compared to PM controls. In DDD patients, NF-κB1⁻DNA binding was positively correlated with nuclear RelA levels. Moreover, NF-κB1⁻DNA binding was positively associated with TRPV1 and MMP-3 gene and SP and TRPV1 protein expression in DDD patients. Our results indicate that the expression of SP and TRPV1 in IVD tissues was associated with NF-κB activation. Moreover, NF-κB may be involved in the generation or maintenance of peripheral pain mechanisms by the regulation of pain-related neuropeptide expression in DDD patients.
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| 7. |
- Andersson, Svante, 1962-, et al.
(författare)
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A Glocal marketing model
- 2009. - 1
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Ingår i: Glocal Marketing. - Lund. - 9789144055558 ; , s. 391-396
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Bokkapitel (refereegranskat)
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| 8. |
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| 9. |
- Andersson, Svante, 1962-, et al.
(författare)
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Early Internationalizing Firms
- 2009. - 1
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Ingår i: Glocal marketing. - Lund. - 9789144055558 ; , s. 45-64
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Bokkapitel (refereegranskat)
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| 10. |
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