Biological amplification of low frequency mutations unravels laboratory culture history of the bio-threat agent Francisella tularensis.

Challenges of investigating a suspected bio attack include establishing if microorganisms have been cultured to produce attack material and to identify their source. Addressing both issues, we have investigated genetic variations that emerge during laboratory culturing of the bacterial pathogen Francisella tularensis. Key aims were to identify genetic variations that are characteristic of laboratory culturing and explore the possibility of using biological amplification to identify genetic variation present at exceedingly low frequencies in a source sample.

A likelihood ratio-based approach for improved source attribution in microbiological forensic investigations.

A common objective in microbial forensic investigations is to identify the origin of a recovered pathogenic bacterium by DNA sequencing. However, there is currently no consensus about how degrees of belief in such origin hypotheses should be quantified, interpreted, and communicated to wider audiences. To fill this gap, we have developed a concept based on calculating probabilistic evidential values for microbial forensic hypotheses.

Accounting for Bacterial Overlap Between Raw Water Communities and Contaminating Sources Improves the Accuracy of Signature-Based Microbial Source Tracking.

Microbial source tracking (MST) analysis is essential to identifying and mitigating the fecal pollution of water resources. The signature-based MST method uses a library of sequences to identify contaminants based on operational taxonomic units (OTUs) that are unique to a certain source. However, no clear guidelines for how to incorporate OTU overlap or natural variation in the raw water bacterial community into MST analyses exist.

Reveals Niche Differences Between Highly Pathogenic and Closely Related Strains of spp.

, a highly virulent bacteria that causes the zoonotic disease tularemia, is considered a potential agent of biological warfare and bioterrorism. Although the host range for several species within the is known, little is known about the natural reservoirs of various species. The lack of knowledge regarding the environmental fates of these pathogens greatly reduces the possibilities for microbial risk assessments.

Association of CD247 (CD3ζ) gene polymorphisms with T1D and AITD in the population of northern Sweden.

Background: T1D and AITD are autoimmune disorders commonly occurring in the same family and even in the same individual. The genetic contribution to these disorders is complex making uncovering of susceptibility genes very challenging. The general aim of this study was to identify loci and genes contributing to T1D/AITD susceptibility.

Eight new genomes and synthetic controls increase the accessibility of rapid melt-MAMA SNP typing of Coxiella burnetii.

The case rate of Q fever in Europe has increased dramatically in recent years, mainly because of an epidemic in the Netherlands in 2009. Consequently, there is a need for more extensive genetic characterization of the disease agent Coxiella burnetii in order to better understand the epidemiology and spread of this disease. Genome reference data are essential for this purpose, but only thirteen genome sequences are currently available.

The phylogeographic pattern of Francisella tularensis in Sweden indicates a Scandinavian origin of Eurosiberian tularaemia.

Previous studies of the causative agent of tularaemia, Francisella tularensis have identified phylogeographic patterns suggestive of environmental maintenance reservoirs. To investigate the phylogeography of tularaemia in Sweden, we selected 163 clinical isolates obtained during 1995-2009 in 10 counties and sequenced one isolate's genome to identify new genetic markers. An improved typing scheme based on two indels and nine SNPs was developed using hydrolysis or TaqMan MGB probe assays.

Increased knowledge of Francisella genus diversity highlights the benefits of optimised DNA-based assays.

Background: Recent advances in sequencing technologies offer promising tools for generating large numbers of genomes, larger typing databases and improved mapping of environmental bacterial diversity. However, DNA-based methods for the detection of Francisella were developed with limited knowledge about genetic diversity. This, together with the high sequence identity between several Francisella species, means there is a high risk of false identification and detection of the highly virulent pathogen Francisella tularensis.

Genome characterisation of the genus Francisella reveals insight into similar evolutionary paths in pathogens of mammals and fish.

Background: Prior to this study, relatively few strains of Francisella had been genome-sequenced. Previously published Francisella genome sequences were largely restricted to the zoonotic agent F. tularensis.

Extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in major depressive disorder (MDD) in patients with an inadequate response to ongoing antidepressant treatment: a multicentre, randomized, double-blind, placebo-controlled study.

This study evaluated once-daily extended-release quetiapine fumarate (quetiapine XR) as adjunctive therapy in patients with major depressive disorder (MDD) with inadequate response to ongoing antidepressant treatment. In this 8-wk (6-wk active treatment/2-wk post-treatment drug-discontinuation/follow-up), multicentre, double-blind, placebo-controlled, Phase III study, 446 patients were randomized to quetiapine XR 150 mg/d, 300 mg/d, or placebo adjunct to ongoing antidepressant treatment. The primary endpoint was the change from randomization to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS) total score.

CT60 genotype does not affect CTLA-4 isoform expression despite association to T1D and AITD in northern Sweden.

Background: Polymorphisms in and around the CTLA-4 gene have previously been associated to T1D and AITD in several populations. One such single nucleotide polymorphism (SNP), CT60, has been reported to affect the expression level ratio of the soluble (sCTLA-4) to full length CTLA-4 (flCTLA-4) isoforms. The aims of our study were to replicate the association previously published by Ueda et al.

TCF7L2 polymorphisms are associated with type 2 diabetes in northern Sweden.

A recent study found association of one microsatellite and five single nucleotide polymorphisms (SNPs) in intron 3 of the TCF7L2 gene with type 2 diabetes (T2D) in the Icelandic, Danish and American populations. The aim of the present study was to investigate if those SNPs were associated to T2D in two (family- and population-based) cohorts from northern Sweden. We genotyped four of the associated SNPs in a case-control cohort consisting of 872 T2D cases and 857 controls matched with respect to age, sex and geographical origin and in a sample of 59 extended families (148 affected and 83 unaffected individuals).

Genome-wide linkage scan of common stroke in families from northern Sweden.

Background And Purpose: Taking advantage of low genetic variations in northern Sweden, we performed a genome-wide linkage scan to investigate the susceptibility loci for common forms of stroke.

Methods: Fifty-six families, containing multiple cases of stroke and whose data had been previously used to replicate linkage to the phosphodiesterase 4D locus on chromosome 5q, were genotyped in a genome-wide scan. Fine mapping was performed, and subsequently 53 additional families from the same region were genotyped over the candidate regions.

Linkage but not association of calpain-10 to type 2 diabetes replicated in northern Sweden.

We present data from a genome-wide scan identifying genetic factors conferring susceptibility to type 2 diabetes. The linkage analysis was based on 59 families from northern Sweden, consisting of a total of 129 cases of type 2 diabetes and 19 individuals with impaired glucose tolerance. Model-free linkage analysis revealed a maximum multipoint logarithm of odds score of 3.

Telomere length and heredity: Indications of paternal inheritance.

Cellular telomere length is linked to replicative life span. Telomere repeats are lost in peripheral blood cells in vivo by age, and women show less telomere attrition than men. Previous reports have indicated that telomere length and chromosome-specific telomere-length patterns partly are inherited.

Linkage of ischemic stroke to the PDE4D region on 5q in a Swedish population.

Background And Purpose: Recent Icelandic studies have demonstrated linkage for common forms of stroke to chromosome 5q12 and association between phosphodiesterase4D (PDE4D) and ischemic stroke. Using a candidate region approach, we wanted to test the validity of these findings in a different population from northern Sweden.

Methods: A total of 56 families with 117 affected individuals were included in the linkage study.

Homozygosity mapping of familial glioma in Northern Sweden.

About 5% of glioma cases are familial. Most glioma families are not ascribed to the well-known glioma predisposing syndromes. One segregation analysis has supported an autosomal recessive gene in glioma families, which could be studied by homozygosity mapping.

A multivariate approach applied to microarray data for identification of genes with cell cycle-coupled transcription.

We have analyzed microarray data using a modeling approach based on the multivariate statistical method partial least squares (PLS) regression to identify genes with periodic fluctuations in expression levels coupled to the cell cycle in the budding yeast, Saccharomyces cerevisiae. PLS has major advantages for analyzing microarray data since it can model data sets with large numbers of variables and with few observations. A response model was derived describing the expression profile over time expected for periodically transcribed genes, and was used to identify budding yeast transcripts with similar profiles.