| 1. |
|
|
| 2. |
- Lees, William, et al.
(author)
-
OGRDB : a reference database of inferred immune receptor genes
- 2020
-
In: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 48:D1, s. 964-970
-
Journal article (peer-reviewed)abstract
- High-throughput sequencing of the adaptive immune receptor repertoire (AIRR-seq) is providing unprecedented insights into the immune response to disease and into the development of immune disorders. The accurate interpretation of AIRR-seq data depends on the existence of comprehensive germline gene reference sets. Current sets are known to be incomplete and unrepresentative of the degree of polymorphism and diversity in human and animal populations. A key issue is the complexity of the genomic regions in which they lie, which, because of the presence of multiple repeats, insertions and deletions, have not proved tractable with short-read whole genome sequencing. Recently, tools and methods for inferring such gene sequences from AIRR-seq datasets have become available, and a community approach has been developed for the expert review and publication of such inferences. Here, we present OGRDB, the Open Germline Receptor Database (https://ogrdb.airr-community.org), a public resource for the submission, review and publication of previously unknown receptor germline sequences together with supporting evidence.
|
|
| 3. |
|
|
| 4. |
- McKay, James D., et al.
(author)
-
Lung cancer susceptibility locus at 5p15.33
- 2008
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:12, s. 1404-1406
-
Journal article (peer-reviewed)abstract
- We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P - 2 x 10(-7) and P = 4 x 10(-6)) and replicated by the independent study series (P = 7 x 10(-5) and P = 0.016). The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology.
|
|
| 5. |
- Palor, Machaela, et al.
(author)
-
Cholesterol sensing by CD81 is important for hepatitis C virus entry
- 2020
-
In: Journal of Biological Chemistry. - : Elsevier. - 0021-9258 .- 1083-351X. ; 295:50, s. 16931-16948
-
Journal article (peer-reviewed)abstract
- CD81 plays a role in a variety of physiological and pathological processes. Recent structural analysis of CD81 indicates that it contains an intramembrane cholesterol-binding pocket and that interaction with cholesterol may regulate a conformational switch in the extracellular domain of CD81. Therefore, CD81 possesses a potential cholesterol sensing mechanism; however, its relevance for protein function is thus far unknown. In this study we investigate CD81 cholesterol sensing in the context of its activity as a receptor for hepatitis C virus. Structure-led mutagenesis of the cholesterol-binding pocket reduced CD81-cholesterol association, but had disparate effects on HCV, both reducing and enhancing CD81 receptor activity. We reasoned that this could be explained by alterations in the consequences of cholesterol binding. To investigate this further we performed molecular dynamic simulations of CD81 with and without cholesterol; this identified an allosteric mechanism by which cholesterol binding regulates the conformation of CD81. To test this, we designed further mutations to force CD81 into either the open (cholesterol unbound) or closed (cholesterol bound) conformation. The open mutant of CD81 exhibited reduced receptor activity whereas the closed mutant was enhanced. These data are consistent with cholesterol switching CD81 between a receptor active and inactive state. CD81 interactome analysis also suggests that conformational switching may modulate the assembly of CD81-partner networks. This work furthers our understanding of the molecular mechanism of CD81 cholesterol sensing, how this relates to HCV entry and CD81's function as a molecular scaffold; these insights are relevant to CD81's varied roles in health and disease.
|
|
| 6. |
- Shepherd, Rosalie H., et al.
(author)
-
Measurement of gas-phase OH radical oxidation and film thickness of organic films at the air-water interface using material extracted from urban, remote and wood smoke aerosol
- 2022
-
In: Environmental Science. - : Royal Society of Chemistry (RSC). - 2634-3606. ; 2:4, s. 574-590
-
Journal article (peer-reviewed)abstract
- The presence of an organic film on a cloud droplet or aqueous aerosol particle has the potential to alter the chemical, optical and physical properties of the droplet or particle. In the study presented, water insoluble organic materials extracted from urban, remote (Antarctica) and wood burning atmospheric aerosol were found to have stable, compressible, films at the air-water interface that were typically similar to 6-18 angstrom thick. These films are reactive towards gas-phase OH radicals and decay exponentially, with bimolecular rate constants for reaction with gas-phase OH radicals of typically 0.08-1.5 x 10(-10) cm(3) molecule(-1) s(-1). These bimolecular rate constants equate to initial OH radical uptake coefficients estimated to be similar to 0.6-1 except woodsmoke (similar to 0.05). The film thickness and the neutron scattering length density of the extracted atmosphere aerosol material (from urban, remote and wood burning) were measured by neutron reflection as they were exposed to OH radicals. For the first time neutron reflection has been demonstrated as an excellent technique for studying the thin films formed at air-water interfaces from materials extracted from atmospheric aerosol samples. Additionally, the kinetics of gas-phase OH radicals with a proxy compound, the lipid 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) was studied displaying significantly different behaviour, thus demonstrating it is not a good proxy for atmospheric materials that may form films at the air-water interface. The atmospheric lifetimes, with respect to OH radical oxidation, of the insoluble organic materials extracted from atmospheric aerosol at the air-water interface were a few hours. Relative to a possible physical atmospheric lifetime of 4 days, the oxidation of these films is important and needs inclusion in atmospheric models. The optical properties of these films were previously reported [Shepherd et al., Atmos. Chem. Phys., 2018, 18, 5235-5252] and there is a significant change in top of the atmosphere albedo for these thin films on core-shell atmospheric aerosol using the film thickness data and confirmation of stable film formation at the air-water interface presented here.
|
|
| 7. |
|
|
