Pitfalls in the phylogenomic evaluation of human disease-causing mutations

A detailed sequence comparison of the MSX homeobox family sheds light on its evolution and identifies new conserved motifs. But in the absence of corroborative genetic data, phylogenomics alone can provide only limited insights into the pathogenicity of heterozygous missense substitutions in human genes

Pediatric Cellulitis: A Red-Hot Concern

Cellulitis and other skin and soft tissue infections are a common reason for children to seek care, both in the primary care setting and the emergency department. Cellulitis is a common skin and soft-tissue infection that is usually caused by streptococci bacteria or, less commonly, Staphylococcus aureus. Most children recover quickly from cellulitis, but a small subset will require hospitalization. Practitioners need to be skilled in the diagnosis and treatment of cellulitis, including recognition of the need for inpatient treatment. However, diagnosis of cellulitis, and exclusion of complicated or other more serious infections, can be challenging. Management of these infections has also been highly variable, resulting in some difficulty identifying the ideal treatment regimen. The goal is to use the antibiotic with the narrowest spectrum for the shortest duration necessary to provide clinical improvement. Research to identify the best treatment for pediatric cellulitis will be important moving forward

Genome sequence of canine herpesvirus

Canine herpesvirus is a widespread alphaherpesvirus that causes a fatal haemorrhagic disease of neonatal puppies. We have used high-throughput methods to determine the genome sequences of three viral strains (0194, V777 and V1154) isolated in the United Kingdom between 1985 and 2000. The sequences are very closely related to each other. The canine herpesvirus genome is estimated to be 125 kbp in size and consists of a unique long sequence (97.5 kbp) and a unique short sequence (7.7 kbp) that are each flanked by terminal and internal inverted repeats (38 bp and 10.0 kbp, respectively). The overall nucleotide composition is 31.6% G+C, which is the lowest among the completely sequenced alphaherpesviruses. The genome contains 76 open reading frames predicted to encode functional proteins, all of which have counterparts in other alphaherpesviruses. The availability of the sequences will facilitate future research on the diagnosis and treatment of canine herpesvirus-associated disease

Spatiotemporal Statistical Downscaling for the Fusion of In-lake and Remote Sensing Data

This paper addresses the problem of fusing data from in-lake monitoring programmes with remote sensing data, through statistical downscaling. A Bayesian hierarchical model is developed, in order to fuse the in-lake and remote sensing data using spatially-varying coefficients. The model is applied to an example dataset of log(chlorophyll-a) data for Lake Erie, one of the Great Lakes of North America

Estimating the volatility of property assets

When an investor is allocating assets between equities, bonds and property, this allocation needs to provide a portfolio with an appropriate risk/return trade-off: for instance, a pension scheme may prefer a robust portfolio that holds its aggregate value in a number of different situations. In order to do this, some estimate needs to be made of the volatility or uncertainty in the property assets, in order to use that in the same way as the volatilities of equities and bonds are used in the allocation. However, property assets are only valued monthly or quarterly (and are sold only rarely) whereas equities and bonds are priced continuously and recorded daily. Currently many actuaries may assume that the volatility of property assets is between those of equities and bonds, but without quantifying it from real data. The challenge for the Study Group is to produce a model for estimating the volatility or uncertainty in property asset values, for use in portfolio planning. The Study Group examined contexts for the use of volatility estimates, particularly in relation to solvency calculations as required by the Financial Services Authority, fund trustees and corporate boards, and it proposed a number of possible approaches. This report summarises that work, and it suggests directions for further investigation

Genome sequences of two pseudorabies virus strains isolated in Greece

Pseudorabies virus (species Suid herpesvirus 1) belongs to the genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae, and is the causative agent of an acute and frequently fatal disease that affects mainly pigs. Here, we report the genome sequences of two strains of this virus isolated in Greece in 2010

Virus and host factors affecting the clinical outcome of bluetongue virus infection

Bluetongue is a major infectious disease of ruminants caused by bluetongue virus (BTV), an arbovirus transmitted by Culicoides. Here, we assessed virus and host factors influencing the clinical outcome of BTV infection using a single experimental framework. We investigated how mammalian host species, breed, age, BTV serotypes, and strains within a serotype, affect the clinical course of bluetongue. Results obtained indicate that in small ruminants there is a marked difference in the susceptibility to clinical disease induced by BTV at the host species level, but less so at the breed level. No major differences in virulence were found between divergent serotypes (BTV-8 and BTV-2). However, we observed striking differences in virulence between closely related strains of the same serotype collected towards the beginning and the end of the European BTV-8 outbreak. As observed previously, differences in disease severity were also observed when animals were infected with either blood from a BTV-infected animal or from the same virus isolated in cell culture. Interestingly, with the exception of two silent mutations, full viral genome sequencing showed identical consensus sequences of the virus before and after cell culture isolation. However, deep sequencing analysis revealed a marked decrease in the genetic diversity of the viral population after passaging in mammalian cells. In contrast, passaging in Culicoides cells increased the overall number of low frequency variants compared to virus never passaged in cell culture. Thus, Culicoides might be a source of new viral variants and viral population diversity can be another factor influencing BTV virulence

Genomic and biologic comparisons of cyprinid herpesvirus 3 strains

Cyprinid herpesvirus 3 (CyHV-3) is the archetypal fish alloherpesvirus and the etiologic agent of a lethal disease in common and koi carp. To date, the genome sequences of only four CyHV-3 isolates have been published, but no comparisons of the biologic properties of these strains have been reported. We have sequenced the genomes of a further seven strains from various geographical sources, and have compared their growth in vitro and virulence in vivo. The major findings were: (i) the existence of the two genetic lineages previously described as European and Asian was confirmed, but inconsistencies between the geographic origin and genotype of some strains were revealed; (ii) potential inter-lineage recombination was detected in one strain, which also suggested the existence of a third, as yet unidentified lineage; (iii) analysis of genetic disruptions led to the identification of non-essential genes and their potential role in virulence; (iv) comparison of the in vitro and in vivo properties of strains belonging to the two lineages revealed that inter-lineage polymorphisms do not contribute to the differences in viral fitness observed; and (v) a negative correlation was observed among strains between viral growth in vitro and virulence in vivo. This study illustrates the importance of coupling genomic and biologic comparisons of viral strains in order to enhance understanding of viral evolution and pathogenesis