| 11. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 12. |
- Dunlop, R. A., et al.
(författare)
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Is Exposure to BMAA a Risk Factor for Neurodegenerative Diseases? : A Response to a Critical Review of the BMAA Hypothesis
- 2021
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Ingår i: Neurotoxicity research. - : Springer. - 1029-8428 .- 1476-3524. ; 39:1, s. 81-106
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Forskningsöversikt (refereegranskat)abstract
- In a literature survey, Chernoff et al. (2017) dismissed the hypothesis that chronic exposure to beta-N-methylamino-L-alanine (BMAA) may be a risk factor for progressive neurodegenerative disease. They question the growing scientific literature that suggests the following: (1) BMAA exposure causes ALS/PDC among the indigenous Chamorro people of Guam; (2) Guamanian ALS/PDC shares clinical and neuropathological features with Alzheimer's disease, Parkinson's disease, and ALS; (3) one possible mechanism for protein misfolds is misincorporation of BMAA into proteins as a substitute for L-serine; and (4) chronic exposure to BMAA through diet or environmental exposures to cyanobacterial blooms can cause neurodegenerative disease. We here identify multiple errors in their critique including the following: (1) their review selectively cites the published literature; (2) the authors reported favorably on HILIC methods of BMAA detection while the literature shows significant matrix effects and peak coelution in HILIC that may prevent detection and quantification of BMAA in cyanobacteria; (3) the authors build alternative arguments to the BMAA hypothesis, rather than explain the published literature which, to date, has been unable to refute the BMAA hypothesis; and (4) the authors erroneously attribute methods to incorrect studies, indicative of a failure to carefully consider all relevant publications. The lack of attention to BMAA research begins with the review's title which incorrectly refers to BMAA as a "non-essential" amino acid. Research regarding chronic exposure to BMAA as a cause of human neurodegenerative diseases is emerging and requires additional resources, validation, and research. Here, we propose strategies for improvement in the execution and reporting of analytical methods and the need for additional and well-executed inter-lab comparisons for BMAA quantitation. We emphasize the need for optimization and validation of analytical methods to ensure that they are fit-for-purpose. Although there remain gaps in the literature, an increasingly large body of data from multiple independent labs using orthogonal methods provides increasing evidence that chronic exposure to BMAA may be a risk factor for neurological illness.
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| 13. |
- 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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| 14. |
- Selroos, O, et al.
(författare)
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National and regional asthma programmes in Europe
- 2015
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Ingår i: European respiratory review : an official journal of the European Respiratory Society. - : European Respiratory Society (ERS). - 1600-0617. ; 24:137, s. 474-83
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Tidskriftsartikel (refereegranskat)abstract
- This review presents seven national asthma programmes to support the European Asthma Research and Innovation Partnership in developing strategies to reduce asthma mortality and morbidity across Europe. From published data it appears that in order to influence asthma care, national/regional asthma programmes are more effective than conventional treatment guidelines. An asthma programme should start with the universal commitments of stakeholders at all levels and the programme has to be endorsed by political and governmental bodies. When the national problems have been identified, the goals of the programme have to be clearly defined with measures to evaluate progress. An action plan has to be developed, including defined re-allocation of patients and existing resources, if necessary, between primary care and specialised healthcare units or hospital centres. Patients should be involved in guided self-management education and structured follow-up in relation to disease severity. The three evaluated programmes show that, thanks to rigorous efforts, it is possible to improve patients' quality of life and reduce hospitalisation, asthma mortality, sick leave and disability pensions. The direct and indirect costs, both for the individual patient and for society, can be significantly reduced. The results can form the basis for development of further programme activities in Europe.
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| 15. |
- Selroos, O, et al.
(författare)
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"National and regional asthma programmes in Europe." Olof Selroos, Maciej Kupczyk, Piotr Kuna, Piotr Łacwik, Jean Bousquet, David Brennan, Susanna Palkonen, Javier Contreras, Mark FitzGerald, Gunilla Hedlin, Sebastian L. Johnston, Renaud Louis, Leanne Metcalf, Samantha Walker, Antonio Moreno-Galdó, Nikolaos G. Papadopoulos, José Rosado-Pinto, Pippa Powell and Tari Haahtela. Eur Respir Rev 2015; 24: 474-483
- 2019
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Ingår i: European respiratory review : an official journal of the European Respiratory Society. - : European Respiratory Society (ERS). - 1600-0617. ; 28:154
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Tidskriftsartikel (refereegranskat)
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| 16. |
- Adderley, Jack D., et al.
(författare)
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Analysis of erythrocyte signalling pathways during Plasmodium falciparum infection identifies targets for host-directed antimalarial intervention
- 2020
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Intracellular pathogens mobilize host signaling pathways of their host cell to promote their own survival. Evidence is emerging that signal transduction elements are activated in a-nucleated erythrocytes in response to infection with malaria parasites, but the extent of this phenomenon remains unknown. Here, we fill this knowledge gap through a comprehensive and dynamic assessment of host erythrocyte signaling during infection with Plasmodium falciparum. We used arrays of 878 antibodies directed against human signaling proteins to interrogate the activation status of host erythrocyte phospho-signaling pathways at three blood stages of parasite asexual development. This analysis reveals a dynamic modulation of many host signalling proteins across parasite development. Here we focus on the hepatocyte growth factor receptor (c-MET) and the MAP kinase pathway component B-Raf, providing a proof of concept that human signaling kinases identified as activated by malaria infection represent attractive targets for antimalarial intervention.
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| 17. |
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| 18. |
- Metcalf, A.J., et al.
(författare)
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Fully programmable two-dimensional pulse shaper for broadband line-by-line amplitude and phase control
- 2013
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Ingår i: Optics Express. - 1094-4087 .- 1094-4087. ; 21:23, s. 28029-28039
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Tidskriftsartikel (refereegranskat)abstract
- We introduce a fully programmable two-dimensional (2D) pulse shaper, able to simultaneously control the amplitude and phase of very fine spectral components over a broad bandwidth. This is achieved by aligning two types of spectral dispersers in a cross dispersion setup: a virtually imaged phased array for accessing fine resolution and a transmission grating for achieving broad bandwidth. We take advantage of the resultant 2D dispersion profile as well as introduce programmability by adding a 2D liquid crystal on silicon spatial light modulator at the masking plane. Our shaper has a resolution of ~3 GHz operating over the entire 'C' band of >5.8 THz. Experimental evidence is provided that highlights the full programmability, fine spectral control, and broad bandwidth operation (limited currently by the bandwidth of the input light). We also show lineby- line manipulation of record 836 comb lines over the C-band. © 2013 Optical Society of America.
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| 19. |
- Metcalf, A. J., et al.
(författare)
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High-Power Broadly Tunable Electrooptic Frequency Comb Generator
- 2013
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Ingår i: IEEE Journal of Selected Topics in Quantum Electronics. - : Institute of Electrical and Electronics Engineers (IEEE). - 1558-4542 .- 1077-260X. ; 19:6
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Tidskriftsartikel (refereegranskat)abstract
- Broadband traveling-wave electrooptic modulators made of lithium niobate have reached a high level of technological maturity. They can provide simultaneously low V pi, sustain high power (both optical and RF) and yet provide low propagation loss. By combining together these features, we present a high-power handling, broadly tunable, electrooptic frequency comb generator. The device produces between 60 and 75 lines within -10 dB bandwidth over its full tuning range-from 6 to 18 GHz- and can handle up to 1 W of optical input power. This optical frequency comb platform is very well suited for applications in RF photonics and optical communications that require independent RF and optical tuning as well as high-repetition rates but moderate bandwidth.
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