Exotic Rickettsiae in Ixodes ricinus: fact or artifact?

Several pathogenic Rickettsia species can be transmitted via Ixodes ricinus ticks to humans and animals. Surveys of I. ricinus for the presence of Rickettsiae using part of its 16S rRNA gene yield a plethora of new and different Rickettsia sequences. Interpreting these data is sometimes difficult and presenting these findings as new or potentially pathogenic Rickettsiae should be done with caution: a recent report suggested presence of a known human pathogen, R. australis, in questing I. ricinus ticks in Europe. A refined analysis of these results revealed that R. helvetica was most likely to be misinterpreted as R. australis. Evidence in the literature is accumulating that rickettsial DNA sequences found in tick lysates can also be derived from other sources than viable, pathogenic Rickettsiae. For example, from endosymbionts, environmental contamination or even horizontal gene transfer

Expected Effect of Deleterious Mutations on Within-Host Adaptation of Pathogens.

UNLABELLED: Adaptation is a common theme in both pathogen emergence, for example, in zoonotic cross-species transmission, and pathogen control, where adaptation might limit the effect of the immune response and antiviral treatment. When such evolution requires deleterious intermediate mutations, fitness ridges and valleys arise in the pathogen's fitness landscape. The effect of deleterious intermediate mutations on within-host pathogen adaptation is examined with deterministic calculations, appropriate for pathogens replicating in large populations with high error rates. The effect of deleterious intermediate mutations on pathogen adaptation is smaller than their name might suggest: when two mutations are required and each individual single mutation is fully deleterious, the pathogen can jump across the fitness valley by obtaining two mutations at once, leading to a proportion of adapted mutants that is 20-fold lower than that in the situation where the fitness of all mutants is neutral. The negative effects of deleterious intermediates are typically substantially smaller and outweighed by the fitness advantages of the adapted mutant. Moreover, requiring a specific mutation order has a substantially smaller effect on pathogen adaptation than the effect of all intermediates being deleterious. These results can be rationalized when the number of routes of mutation available to the pathogen is calculated, providing a simple approach to estimate the effect of deleterious mutations. The calculations discussed here are applicable when the effect of deleterious mutations on the within-host adaptation of pathogens is assessed, for example, in the context of zoonotic emergence, antigenic escape, and drug resistance. IMPORTANCE: Adaptation is critical for pathogens after zoonotic transmission into a new host species or to achieve antigenic immune escape and drug resistance. Using a deterministic approach, the effects of deleterious intermediate mutations on pathogen adaptation were calculated while avoiding commonly made simplifications that do not apply to large pathogen populations replicating with high mutation rates. Perhaps unexpectedly, pathogen adaptation does not halt when the intermediate mutations are fully deleterious. The negative effects of deleterious mutations are substantially outweighed by the fitness gains of adaptation. To gain an understanding of the effect of deleterious mutations on pathogen adaptation, a simple approach that counts the number of routes available to the pathogen with and without deleterious intermediate mutations is introduced. This methodology enables a straightforward calculation of the proportion of the pathogen population that will cross a fitness valley or traverse a fitness ridge, without reverting to more complicated mathematical models.This work was supported by the award of a Fellowship in Biomedical Informatics from the Medical Research Council UK (MR/K021885/1) and a Junior Research Fellowship from Homerton College Cambridge to JMF; and the award of HHSN272201400008C (NIAID Centres of Excellence for Influenza Research and Surveillance) to the Center for Pathogen Evolution.This is the author accepted manuscript. The final version is available from American Society for Microbiology at http://jvi.asm.org/content/early/2015/06/23/JVI.00832-15.abstract?cited-by=yes&legid=jvi;JVI.00832-15v1

How Dysarthric Prosody Impacts Naïve Listeners’ Recognition

The class of speech disorders known as dysarthria arise from disturbances in muscular control over the speech mechanism caused by damage of the central or peripheral nervous system. Dysarthria is typically classified into one of six classes, each corresponding to a different neurological disorder with distinct prosodic cues [3]. The assumption in this classification is that dysarthric speech can be classified implicit on the basis of perception. In this study, we investigate how accurately naïve listeners can recognize stress and intonation in dysarthric speech, and if different neurological disorders impact the ability to convey meaning with these same two cues. To those ends, we collected speech data from Dutch speakers diagnosed with cerebellar lesions (ataxic dysarthria), Parkinson’s Disease (hypokinetic dysarthria), Multiple Sclerosis (mixed classes of dysarthria) and from a healthy control group. Thirteen naïve Dutch listeners participated in the perceptual experiment which targeted recognition of intended realization of four prosodic functions: lexical stress, sentence type, boundary marking and focus. We analyzed recognition accuracy for different groups and performed acoustic analyses to check for fundamental frequency trajectories. Results attest to different accuracy recognition results for different disease groups. The sentence type recognition task was the most sensitive of all tasks for differentiating different diseases both on perceptual and acoustic levels of analysis.</p

Psychotic experiences, working memory, and the developing brain: a multimodal neuroimaging study

Psychotic experiences (PEs) occur in the general population, especially in children and adolescents, and are associated with poor psychosocial outcomes, impaired cognition, and increased risk of transition to psychosis. It is unknown how the presence and persistence of PEs during early adulthood affects cognition and brain function. The current study assessed working memory as well as brain function and structure in 149 individuals, with and without PEs, drawn from a population cohort. Observer-rated PEs were classified as persistent or transient on the basis of longitudinal assessments. Working memory was assessed using the n-back task during fMRI. Dynamic causal modeling (DCM) was used to characterize frontoparietal network configuration and voxel-based morphometry was utilized to examine gray matter. Those with persistent, but not transient, PEs performed worse on the n-back task, compared with controls, yet showed no significant differences in regional brain activation or brain structure. DCM analyses revealed greater emphasis on frontal connectivity within a frontoparietal network in those with PEs compared with controls. We propose that these findings portray an altered configuration of working memory function in the brain, potentially indicative of an adaptive response to atypical development associated with the manifestation of PEs

The Genetic Diversity of Rickettsiella Symbionts in Ixodes ricinus Throughout Europe

Rickettsiella species are bacterial symbionts that are present in a great variety of arthropod species, including ixodid ticks. However, little is known about their genetic diversity and distribution in Ixodes ricinus, as well as their relationship with other tick-associated bacteria. In this study, we investigated the occurrence and the genetic diversity of Rickettsiella spp. in I. ricinus throughout Europe and evaluated any preferential and antagonistic associations with Candidatus Midichloria mitochondrii and the pathogens Borrelia burgdorferi sensu lato and Borrelia miyamotoi. Rickettsiella spp. were detected in most I. ricinus populations investigated, encompassing a wide array of climate types and environments. The infection prevalence significantly differed between geographic locations and was significantly higher in adults than in immature life stages. Phylogenetic investigations and protein characterization disclosed four Rickettsiella clades (I-IV). Close phylogenetic relations were observed between Rickettsiella strains of I. ricinus and other arthropod species. Isolation patterns were detected for Clades II and IV, which were restricted to specific geographic areas. Lastly, although coinfections occurred, we did not detect significant associations between Rickettsiella spp. and the other tick-associated bacteria investigated. Our results suggest that Rickettsiella spp. are a genetically and biologically diverse facultative symbiont of I. ricinus and that their distribution among tick populations could be influenced by environmental components

Tekenradar.nl : tekenbeten, ziekte van Lyme en andere tekenoverdraagbare aandoeningen

Tekenradar.nl is een web-platform voor onderzoek naar teken, de ziekte van Lyme en andere tekenoverdraagbare aandoeningen. In een van de nog lopende onderzoeken wordt onderzocht in hoeverre preventieve antibiotica na een tekenbeet helpt om de ziekte van Lyme te voorkomen. In een ander onderzoek naar teken, die in 2012 zijn ingezameld via Tekenradar, is gekeken hoe vaak de teken naast Borrelia burgdorferi s.l. besmet waren met Borrelia miyamotoi. Deze laatste is een bacterie waarvan nu nog onduidelijk is in hoeverre die ziekte kan veroorzaken onder de Nederlandse bevolking

Volumetric, relaxometric and diffusometric correlates of psychotic experiences in a non-clinical sample of young adults

BACKGROUND: Grey matter (GM) abnormalities are robust features of schizophrenia and of people at ultra high-risk for psychosis. However the extent to which neuroanatomical alterations are evident in non-clinical subjects with isolated psychotic experiences is less clear. METHODS: Individuals (mean age 20 years) with (n = 123) or without (n = 125) psychotic experiences (PEs) were identified from a population-based cohort. All underwent T1-weighted structural, diffusion and quantitative T1 relaxometry MRI, to characterise GM macrostructure, microstructure and myelination respectively. Differences in quantitative GM structure were assessed using voxel-based morphometry (VBM). Binary and ordinal models of PEs were tested. Correlations between socioeconomic and other risk factors for psychosis with cortical GM measures were also computed. RESULTS: GM volume in the left supra-marginal gyrus was reduced in individuals with PEs relative to those with no PEs. The greater the severity of PEs, the greater the reduction in T1 relaxation rate (R1) across left temporoparietal and right pre-frontal cortices. In these regions, R1 was positively correlated with maternal education and inversely correlated with general psychopathology. CONCLUSIONS: PEs in non-clinical subjects were associated with regional reductions in grey-matter volume reduction and T1 relaxation rate. The alterations in T1 relaxation rate were also linked to the level of general psychopathology. Follow up of these subjects should clarify whether these alterations predict the later development of an ultra high-risk state or a psychotic disorder

Absence of zoonotic Bartonella species in questing ticks: First detection of Bartonella clarridgeiae and Rickettsia felis in cat fleas in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Awareness for flea- and tick-borne infections has grown in recent years and the range of microorganisms associated with these ectoparasites is rising. <it>Bartonella henselae</it>, the causative agent of Cat Scratch Disease, and other <it>Bartonella </it>species have been reported in fleas and ticks. The role of <it>Ixodes ricinus </it>ticks in the natural cycle of <it>Bartonella </it>spp. and the transmission of these bacteria to humans is unclear. <it>Rickettsia </it>spp. have also been reported from as well ticks as also from fleas. However, to date no flea-borne <it>Rickettsia </it>spp. were reported from the Netherlands. Here, the presence of <it>Bartonellaceae </it>and <it>Rickettsiae </it>in ectoparasites was investigated using molecular detection and identification on part of the gltA- and 16S rRNA-genes.</p> <p>Results</p> <p>The zoonotic <it>Bartonella clarridgeiae </it>and <it>Rickettsia felis </it>were detected for the first time in Dutch cat fleas. <it>B. henselae </it>was found in cat fleas and <it>B. schoenbuchensis </it>in ticks and keds feeding on deer. Two <it>Bartonella </it>species, previously identified in rodents, were found in wild mice and their fleas. However, none of these microorganisms were found in 1719 questing <it>Ixodes ricinus </it>ticks. Notably, the gltA gene amplified from DNA lysates of approximately 10% of the questing nymph and adult ticks was similar to that of an uncultured <it>Bartonella-</it>related species found in other hard tick species. The gltA gene of this <it>Bartonella-</it>related species was also detected in questing larvae for which a 16S rRNA gene PCR also tested positive for "<it>Candidatus </it>Midichloria mitochondrii"<it/>. The gltA-gene of the <it>Bartonella-</it>related species found in <it>I. ricinus </it>may therefore be from this endosymbiont.</p> <p>Conclusions</p> <p>We conclude that the risk of acquiring Cat Scratch Disease or a related bartonellosis from questing ticks in the Netherlands is negligible. On the other hand fleas and deer keds are probable vectors for associated <it>Bartonella </it>species between animals and might also transmit <it>Bartonella </it>spp. to humans.</p

Neural Correlates of Theory of Mind Are Preserved in Young Women With Anorexia Nervosa

People with anorexia nervosa (AN) commonly exhibit social difficulties, which may be related to problems with understanding the perspectives of others, commonly known as Theory of Mind (ToM) processing. However, there is a dearth of literature investigating the neural basis of these differences in ToM and at what age they emerge. This study aimed to test for differences in the neural correlates of ToM processes in young women with AN, and young women weight-restored (WR) from AN, as compared to healthy control participants (HC). Based on previous findings in AN, we hypothesized that young women with current or prior AN, as compared to HCs, would exhibit a reduced neural response in the medial prefrontal cortex (mPFC), the inferior frontal gyrus, and the temporo-parietal junction (TPJ) whilst completing a ToM task. We recruited 73 young women with AN, 45 WR young women, and 70 young women without a history of AN to take part in the current study. Whilst undergoing a functional magnetic resonance imaging (fMRI) scan, participants completed the Frith-Happé task, which is a commonly used measure of ToM with demonstrated reliability and validity in adult populations. In this task, participants viewed the movements of triangles, which depicted either action movements, simple interactions, or complex social interactions. Viewing trials with more complex social interactions in the Frith-Happé task was associated with increased brain activation in regions including the right TPJ, the bilateral mPFC, the cerebellum, and the dorsolateral prefrontal cortex. There were no group differences in neural activation in response to the ToM contrast. Overall, these results suggest that the neural basis of spontaneous mentalizing is preserved in most young women with AN

Pathways of Resistance to Thymineless Death in Escherichia coli and the Function of UvrD

Thymineless death (TLD) is the rapid loss of viability in bacterial, yeast, and human cells starved of thymine. TLD is the mode of action of common anticancer drugs and some antibiotics. TLD in Escherichia coli is accompanied by blocked replication and chromosomal DNA loss and recent work identified activities of recombination protein RecA and the SOS DNA-damage response as causes of TLD. Here, we examine the basis of hypersensitivity to thymine deprivation (hyper-TLD) in mutants that lack the UvrD helicase, which opposes RecA action and participates in some DNA repair mechanisms, RecBCD exonuclease, which degrades double-stranded linear DNA and works with RecA in double-strand-break repair and SOS induction, and RuvABC Holliday-junction resolvase. We report that hyper-TLD in ∆uvrD cells is partly RecA dependent and cannot be attributed to accumulation of intermediates in mismatch repair or nucleotide-excision repair. These data imply that both its known role in opposing RecA and an additional as-yet-unknown function of UvrD promote TLD resistance. The hyper-TLD of ∆ruvABC cells requires RecA but not RecQ or RecJ. The hyper-TLD of recB cells requires neither RecA nor RecQ, implying that neither recombination nor SOS induction causes hyper-TLD in recB cells, and RecQ is not the sole source of double-strand ends (DSEs) during TLD, as previously proposed; models are suggested. These results define pathways by which cells resist TLD and suggest strategies for combating TLD resistance during chemotherapies