Modeling DNA Structure, Elasticity and Deformations at the Base-pair Level

We present a generic model for DNA at the base-pair level. We use a variant of the Gay-Berne potential to represent the stacking energy between neighboring base-pairs. The sugar-phosphate backbones are taken into account by semi-rigid harmonic springs with a non-zero spring length. The competition of these two interactions and the introduction of a simple geometrical constraint leads to a stacked right-handed B-DNA-like conformation. The mapping of the presented model to the Marko-Siggia and the Stack-of-Plates model enables us to optimize the free model parameters so as to reproduce the experimentally known observables such as persistence lengths, mean and mean squared base-pair step parameters. For the optimized model parameters we measured the critical force where the transition from B- to S-DNA occurs to be approximately $140{pN}$. We observe an overstretched S-DNA conformation with highly inclined bases that partially preserves the stacking of successive base-pairs.Comment: 15 pages, 25 figures. submitted to PR

The interaction of human microbial pathogens, particulate material and nutrients in estuarine environments and their impacts on recreational and shellfish waters

Anthropogenic activities have increased the load of faecal bacteria, pathogenic viruses and nutrients in rivers, estuaries and coastal areas through point and diffuse sources such as sewage discharges and agricultural runoff. These areas are used by humans for both commercial and recreational activities and are therefore protected by a range of European Directives. If water quality declines in these zones, significant economic losses can occur. Identifying the sources of pollution, however, is notoriously difficult due to the ephemeral nature of discharges, their diffuse source, and uncertainties associated with transport and transformation of the pollutants through the freshwater–marine interface. Further, significant interaction between nutrients, microorganisms and particulates can occur in the water column making prediction of the fate and potential infectivity of human pathogenic organisms difficult to ascertain. This interaction is most prevalent in estuarine environments due to the formation of flocs (suspended sediment) at the marine-freshwater interface. A range of physical, chemical and biological processes can induce the co-flocculation of microorganisms, organic matter and mineral particles resulting in pathogenic organisms becoming potentially protected from a range of biotic (e.g. predation) and abiotic stresses (e.g. UV, salinity). These flocs contain and retain macro- and micro- nutrients allowing the potential survival, growth and transfer of pathogenic organisms to commercially sensitive areas (e.g. beaches, shellfish harvesting waters). The flocs can either be transported directly to the coastal environment or can become deposited in the estuary forming cohesive sediments where pathogens can survive for long periods. Especially in response to storms, these sediments can be subsequently remobilised releasing pulses of potential pathogenic organisms back into the water column leading to contamination of marine waters long after the initial contamination event occurred. Further work, however, is still required to understand and predict the potential human infectivity of pathogenic organisms alongside the better design of early warning systems and surveillance measures for risk assessment purposes

EPO does not promote interaction between the erythropoietin and beta-common receptors

A direct interaction between the erythropoietin (EPOR) and the beta-common (βc) receptors to form an Innate Repair Receptor (IRR) is controversial. On one hand, studies have shown a functional link between EPOR and βc receptor in tissue protection while others have shown no involvement of the βc receptor in tissue repair. To date there is no biophysical evidence to confirm a direct association of the two receptors either in vitro or in vivo. We investigated the existence of an interaction between the extracellular regions of EPOR and the βc receptor in silico and in vitro (either in the presence or absence of EPO or EPO-derived peptide ARA290). Although a possible interaction between EPOR and βc was suggested by our computational and genomic studies, our in vitro biophysical analysis demonstrates that the extracellular regions of the two receptors do not specifically associate. We also explored the involvement of the βc receptor gene (Csf2rb) under anaemic stress conditions and found no requirement for the βc receptor in mice. In light of these studies, we conclude that the extracellular regions of the EPOR and the βc receptor do not directly interact and that the IRR is not involved in anaemic stress.Karen S. Cheung Tung Shing, Sophie E. Broughton, Tracy L. Nero, Kevin Gillinder, Melissa D. Ilsley, Hayley Ramshaw, Angel F. Lopez, Michael D. W. Griffin, Michael W. Parker, Andrew C. Perkins, Urmi Dhaga

7th Drug hypersensitivity meeting: part two

No abstract availabl

Age at first birth in women is genetically associated with increased risk of schizophrenia

Prof. Paunio on PGC:n jäsenPrevious studies have shown an increased risk for mental health problems in children born to both younger and older parents compared to children of average-aged parents. We previously used a novel design to reveal a latent mechanism of genetic association between schizophrenia and age at first birth in women (AFB). Here, we use independent data from the UK Biobank (N = 38,892) to replicate the finding of an association between predicted genetic risk of schizophrenia and AFB in women, and to estimate the genetic correlation between schizophrenia and AFB in women stratified into younger and older groups. We find evidence for an association between predicted genetic risk of schizophrenia and AFB in women (P-value = 1.12E-05), and we show genetic heterogeneity between younger and older AFB groups (P-value = 3.45E-03). The genetic correlation between schizophrenia and AFB in the younger AFB group is -0.16 (SE = 0.04) while that between schizophrenia and AFB in the older AFB group is 0.14 (SE = 0.08). Our results suggest that early, and perhaps also late, age at first birth in women is associated with increased genetic risk for schizophrenia in the UK Biobank sample. These findings contribute new insights into factors contributing to the complex bio-social risk architecture underpinning the association between parental age and offspring mental health.Peer reviewe