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| 2. |
- Besharat, Zahra, et al.
(författare)
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Mixed monolayers of alkane thiols with polar terminal group on gold : Investigation of structure dependent surface properties
- 2016
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 484, s. 279-290
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Tidskriftsartikel (refereegranskat)abstract
- Adsorption of thiols with cationic or anionic terminal group on gold has been studied from mixed solutions of 11-Amino-1-undecanethiol (AUT) and 3-Mercaptopropionic acid (MPA) using Quartz Crystal Microbalance with Dissipation (QCM-D), X-ray Photoelectron Spectroscopy (XPS), atomic force microscopy (AFM) and contact angles. The goal is to probe the nature of such layers, and the additivity or otherwise of the pH responsiveness, with a view to evaluate their suitability as smart materials. For each of the two pure (unmixed) cases, ordered molecular monolayers are formed with sulfur binding to gold and the alkane chain pointing out from the surface as expected. Adsorption from the thiol mixtures, however, leads to a more complex behaviour. The surface concentration of thiols from the mixtures, as determined by QCM-D, is considerably lower than for the pure cases and it reaches a minimum at a 3:1 MPA/AUT relative concentration in the solution. The XPS results confirm a reduction in adsorbed amount in mixtures with the lowest overall intensity for the 3:1 ratio. Monolayers formed from mixtures display a wettability which is much lower and less pH sensitive. Collectively these results confirm that for adsorption from mixed systems, the configuration is completely different. Complex formation in the mixed solutions leads to the adsorption of molecules parallel to the surface in an axially in-plane configuration. This parallel layer of thiols is mechanically relatively robust to nano-shaving based on AFM measurements. These results will have a significant impact on the design of biomimetic surface coatings particularly when mixtures of oppositely charged molecules are present on the surface, as is commonly the case in biological, proteinaceous surfaces (e.g. hair and skin).
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| 3. |
- Martin, Océane C.B., et al.
(författare)
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Influence of the microenvironment on modulation of the host response by typhoid toxin
- 2021
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Ingår i: Cell Reports. - : Cell Press. - 2211-1247. ; 35:1
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial genotoxins cause DNA damage in eukaryotic cells, resulting in activation of the DNA damage response (DDR) in vitro. These toxins are produced by Gram-negative bacteria, enriched in the microbiota of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. However, their role in infection remains poorly characterized. We address the role of typhoid toxin in modulation of the host-microbial interaction in health and disease. Infection with a genotoxigenic Salmonella protects mice from intestinal inflammation. We show that the presence of an active genotoxin promotes DNA fragmentation and senescence in vivo, which is uncoupled from an inflammatory response and unexpectedly associated with induction of an anti-inflammatory environment. The anti-inflammatory response is lost when infection occurs in mice with acute colitis. These data highlight a complex context-dependent crosstalk between bacterial-genotoxin-induced DDR and the host immune response, underlining an unexpected role for bacterial genotoxins.
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| 4. |
- Rawstron, Andy C., et al.
(författare)
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Monoclonal B-cell lymphocytosis in a hospital-based UK population and a rural Ugandan population : a cross-sectional study
- 2017
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Ingår i: The Lancet Haematology. - 2352-3026. ; 4:7, s. E334-E340
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Tidskriftsartikel (refereegranskat)abstract
- Background Reported incidence of B-cell malignancies shows substantial geographical variation, being more common in the Americas and Europe than in Africa. This variation might reflect differences in diagnostic capability, inherited susceptibility, and infectious exposures. Monoclonal B-cell lymphocytosis (MBL) is a precursor lesion that can be screened for in apparently healthy people, allowing comparison of prevalence across different populations independently of health-care provision. We aimed to compare the prevalence and phenotypic characteristics of MBL in age-and-sex-matched populations from rural Uganda and the UK. Methods In this cross-sectional study, we recruited volunteers aged at least 45 years who were seronegative for HIV-1 from the established Ugandan General Population Cohort and obtained their whole-blood samples. We also obtained blood samples from anonymised waste material of age-and-sex-matched individuals (aged >45 years, with a normal blood count and no history of cancer) in the UK. We used flow cytometry to determine the presence of MBL, defined according to standard diagnostic criteria, in the samples and compared differences in the proportion of cases with chronic lymphocytic leukaemia (CLL)-phenotype MBL and CD5-negative MBL, as well as differences in absolute monoclonal B-cell count between the two cohorts. Findings Between Jan 15 and Dec 18, 2012, we obtained samples from 302 Ugandan volunteers and 302 UK individuals who were matched by age and sex to the Ugandan population. Overall MBL prevalence was higher in the Ugandan participants (42 [14%] individuals) than in the UK cohort (25 [8%]; p=0.038). CLL-phenotype MBL was detected in three (1%) Ugandan participants and 21 (7%) UK participants (p=0.00021); all three Ugandan participants had absolute monoclonal B-cell count below one cell per mu L, whereas the 21 UK participants had a median absolute number of circulating neoplastic cells of 4.6 (IQR 2-12) cells per mu L. The prevalence of CD5-negative MBL was higher in the Ugandan cohort (41 [14%], of whom two [5%] also had CLL-phenotype MBL) than in the UK cohort (six [2%], of whom two [33%] also had CLL-phenotype MBL; p<0.0001), but the median absolute B-cell count was similar (227 [IQR 152-345] cells per mu L in the Ugandan cohort vs 135 [105-177] cells per mu L in the UK cohort; p=0.13). Interpretation MBL is common in both Uganda and the UK, but the substantial phenotypic differences might reflect fundamental differences in the pathogenesis of B-cell lymphoproliferative disorders.
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| 5. |
- Wilhelm, MT, et al.
(författare)
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Isoform-specific p73 knockout mice reveal a novel role for delta Np73 in the DNA damage response pathway
- 2010
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Ingår i: Genes & development. - : Cold Spring Harbor Laboratory. - 1549-5477 .- 0890-9369. ; 24:6, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- Mice with a complete deficiency of p73 have severe neurological and immunological defects due to the absence of all TAp73 and ΔNp73 isoforms. As part of our ongoing program to distinguish the biological functions of these isoforms, we generated mice that are selectively deficient for the ΔNp73 isoform. Mice lacking ΔNp73 (ΔNp73−/− mice) are viable and fertile but display signs of neurodegeneration. Cells from ΔNp73−/− mice are sensitized to DNA-damaging agents and show an increase in p53-dependent apoptosis. When analyzing the DNA damage response (DDR) in ΔNp73−/− cells, we discovered a completely new role for ΔNp73 in inhibiting the molecular signal emanating from a DNA break to the DDR pathway. We found that ΔNp73 localizes directly to the site of DNA damage, can interact with the DNA damage sensor protein 53BP1, and inhibits ATM activation and subsequent p53 phosphorylation. This novel finding may explain why human tumors with high levels of ΔNp73 expression show enhanced resistance to chemotherapy.
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| 6. |
- Zhu, Jian-Xin, et al.
(författare)
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Electronic correlation and magnetism in the ferromagnetic metal Fe3GeTe2
- 2016
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Ingår i: PHYSICAL REVIEW B. - : American Physical Society. - 2469-9950. ; 93:14
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Tidskriftsartikel (refereegranskat)abstract
- Motivated by the search for design principles of rare-earth-free strong magnets, we present a study of electronic structure and magnetic properties of the ferromagnetic metal Fe3GeTe2 within the local-density approximation (LDA) of the density-functional theory, and its combination with dynamical mean-field theory (DMFT). To compare these calculations, we measure magnetic and thermodynamic properties as well as x-ray magnetic circular dichroism and the photoemission spectrum of single-crystal Fe3GeTe2. We find that the experimentally determined Sommerfeld coefficient is enhanced by an order of magnitude with respect to the LDA value. This enhancement can be partially explained by LDA+DMFT. In addition, the inclusion of dynamical electronic correlation effects provides the experimentally observed magnetic moments, and the spectral density is in better agreement with photoemission data. These results establish the importance of electronic correlations in this ferromagnet.
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