Molecular dynamics study of accelerated ion-induced shock waves in biological media

We present a molecular dynamics study of the effects of carbon- and iron-ion induced shock waves in DNA duplexes in liquid water. We use the CHARMM force field implemented within the MBN Explorer simulation package to optimize and equilibrate DNA duplexes in liquid water boxes of different sizes and shapes. The translational and vibrational degrees of freedom of water molecules are excited according to the energy deposited by the ions and the subsequent shock waves in liquid water are simulated. The pressure waves generated are studied and compared with an analytical hydrodynamics model which serves as a benchmark for evaluating the suitability of the simulation boxes. The energy deposition in the DNA backbone bonds is also monitored as an estimation of biological damage, something which is not possible with the analytical model

Discrimination of strains of Salmonella enteritidis with differing levels of virulence by an in vitro glass adherence test

The objective of this study was the in vitro differentiation of isolates of Salmonella enteritidis whose virulences differed in a chick model. A total of 14 strains of S. enteritidis were isolated from either the environment, dairy products, or infected patients. The isolates could be divided into two groups on the basis of their virulence (50% lethal dose) in chickens infected intraperitoneally. When the strains were incubated in adherence test medium (Spanish patent 9700408), only the virulent strains produced aggregates and formed visible filaments attached to the glass tube. These results suggest, although for a limited number of strains, that aggregation in such a medium could be used as a diagnostic tool to discriminate virulent strains of S. enteritidis

Increasing prevalence of a fluoroquinolone resistance mutation amongst Campylobacter jejuni isolates from four human infectious intestinal disease studies in the United Kingdom

Background: Campylobacter jejuni is the most common bacterial cause of human infectious intestinal disease. Methods: We genome sequenced 601 human C. jejuni isolates, obtained from two large prospective studies of infectious intestinal disease (IID1 [isolates from 1993–1996; n = 293] and IID2 [isolates from 2008–2009; n = 93]), the INTEGRATE project [isolates from 2016–2017; n = 52] and the ENIGMA project [isolates from 2017; n = 163]. Results: There was a significant increase in the prevalence of the T86I mutation conferring resistance to fluoroquinolone between each of the three later studies (IID2, INTEGRATE and ENIGMA) and IID1. Although the distribution of major multilocus sequence types (STs) was similar between the studies, there were changes in both the abundance of minority STs associated with the T86I mutation, and the abundance of clones within single STs associated with the T86I mutation. Discussion: Four population-based studies of community diarrhoea over a 25 year period revealed an increase over time in the prevalence of the T86I amongst isolates of C. jejuni associated with human gastrointestinal disease in the UK. Although associated with many STs, much of the increase is due to the expansion of clones associated with the resistance mutation

Threshold analyses and Lorentz violation

In the context of threshold investigations of Lorentz violation, we discuss the fundamental principle of coordinate invariance, the role of an effective dynamical framework, and the conditions of positivity and causality. Our analysis excludes a variety of previously considered Lorentz-breaking parameters and opens an avenue for viable dispersion-relation investigations of Lorentz violation.Comment: 9 page

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele