Lambda-prophage induction modeled as a cooperative failure mode of lytic repression

We analyze a system-level model for lytic repression of lambda-phage in E. coli using reliability theory, showing that the repressor circuit comprises 4 redundant components whose failure mode is prophage induction. Our model reflects the specific biochemical mechanisms involved in regulation, including long-range cooperative binding, and its detailed predictions for prophage induction in E. coli under ultra-violet radiation are in good agreement with experimental data.Comment: added referenc

JMM Profile: Usutu virus.

Usutu virus (USUV) is an emerging arbovirus belonging to the family Flaviviridae, genus Flavivirus. It is maintained in an enzootic cycle, with mosquitos as the vector and birds as the main amplifying host. Humans, and other mammals such as horses, are dead-end hosts. The virus was originally detected in sub-Saharan Africa, but in the past two decades has spread across Europe. In certain bird species, such as the Eurasian blackbird (Turdus merula), USUV is extremely virulent and can be fatal. Human infection is rare and often asymptomatic, but multiple short-term neurological diseases have been reported, highlighting its public-health risk

Early specialist orthotic interventions for the lower limb in adult stroke patients: a systematic literature review

Background: Stroke is a leading cause of long-term disability worldwide, estimated to affect up to 50% of stroke survivors. Many stroke survivors use orthotic splints and braces to help address difficulties with mobility and gait dysfunction both early after the stroke event and longer-term.Objectives: The aim of this systematic review was to identify, synthesise and appraise the evidence on early orthotic involvement for the lower limb following stroke.Study design: Systematic literature reviewMethods We conducted a systematic search of electronic databases including: AMED (1985 to present; CINAHL (1982 to present); EMBASE (1980 to present); MEDLINE (1949 to present); PsycINFO (1967 to present). The search took place on 18/10/2019. Included studies evaluated an early orthotic intervention designed to either promote mobility or reduce secondary complications after stroke. Articles were screened for inclusion by two independent reviewers.Results: This review included six articles from one research group in the Netherlands. Methodological quality was considered good in each of the included studies. Limitations include small sample size, restricted descriptions of the intervention and short-term follow-ups.Conclusion: This systematic review suggests that earlier lower limb orthotic interventions can result in improved walking speed and balance, and enhanced ability to perform activities of daily living in the early weeks post-stroke. Future research would benefit from considering wider orthotic and orthotist intervention with larger sample sizes and longer-term outcomes

A variant in LIN28B is associated with 2D:4D finger-length ratio, a putative retrospective biomarker of prenatal testosterone exposure

The ratio of the lengths of an individual's second to fourth digit (2D:4D) is commonly used as a noninvasive retrospective biomarker for prenatal androgen exposure. In order to identify the genetic determinants of 2D:4D, we applied a genome-wide association approach to 1507 11-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) in whom 2D:4D ratio had been measured, as well as a sample of 1382 12- to 16-year-olds from the Brisbane Adolescent Twin Study. A meta-analysis of the two scans identified a single variant in the LIN28B gene that was strongly associated with 2D:4D (rs314277: p = 4.1 108) and was subsequently independently replicated in an additional 3659 children from the ALSPAC cohort (p = 1.53 106). The minor allele of the rs314277 variant has previously been linked to increased height and delayed age at menarche, but in our study it was associated with increased 2D:4D in the direction opposite to that of previous reports on the correlation between 2D:4D and age at menarche. Our findings call into question the validity of 2D:4D as a simplistic retrospective biomarker for prenatal testosterone exposure

Sequences related to Chimay rhabdovirus are widely distributed in Ixodes ricinus ticks across England and Wales

Ticks are the main arthropod vector of pathogens to humans and livestock in the British Isles. Despite their role as a vector of disease, many aspects of tick biology, ecology, and microbial association are poorly understood. To address this, we investigated the composition of the microbiome of adult and nymphal Ixodes ricinus ticks. The ticks were collected on a dairy farm in Southwest England and RNA extracted for whole genome sequencing. Sequences were detected from a range of microorganisms, particularly tick-associated viruses, bacteria, and nematodes. A majority of the viruses were attributed to phlebo-like and nairo-like virus groups, demonstrating a high degree of homology with the sequences present in I. ricinus from mainland Europe. A virus sharing a high sequence identity with Chimay rhabdovirus, previously identified in ticks from Belgium, was detected. Further investigations of I. ricinus ticks collected from additional sites in England and Wales also identified Chimay rhabdovirus viral RNA with varying prevalence in all tick populations. This suggests that Chimay rhabdovirus has a wide distribution and highlights the need for an extended exploration of the tick microbiome in the United Kingdom (UK)

Defining the geographical range of the plasmodium knowlesi reservoir

Background: The simian malaria parasite, Plasmodium knowlesi, can cause severe and fatal disease in humans yet it is rarely included in routine public health reporting systems for malaria and its geographical range is largely unknown. Because malaria caused by P. knowlesi is a truly neglected tropical disease, there are substantial obstacles to defining the geographical extent and risk of this disease. Information is required on the occurrence of human cases in different locations, on which non-human primates host this parasite and on which vectors are able to transmit it to humans. We undertook a systematic review and ranked the existing evidence, at a subnational spatial scale, to investigate the potential geographical range of the parasite reservoir capable of infecting humans.Methodology/Principal Findings: After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region.Conclusions/Significance: We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment

Data mashups: potential contribution to decision support on climate change and health.

notes: PMCID: PMC3945564This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Linking environmental, socioeconomic and health datasets provides new insights into the potential associations between climate change and human health and wellbeing, and underpins the development of decision support tools that will promote resilience to climate change, and thus enable more effective adaptation. This paper outlines the challenges and opportunities presented by advances in data collection, storage, analysis, and access, particularly focusing on "data mashups". These data mashups are integrations of different types and sources of data, frequently using open application programming interfaces and data sources, to produce enriched results that were not necessarily the original reason for assembling the raw source data. As an illustration of this potential, this paper describes a recently funded initiative to create such a facility in the UK for use in decision support around climate change and health, and provides examples of suitable sources of data and the purposes to which they can be directed, particularly for policy makers and public health decision makers.UK Medical Research CouncilUK Natural Environment Research CouncilEuropean Regional Development Fund Programme 2007 to 2013European Social Fund Convergence Programme for Cornwall and the Isles of Scill

How will climate change pathways and mitigation options alter incidence of vector-borne diseases? A framework for leishmaniasis in South and Meso-America

The enormous global burden of vector-borne diseases disproportionately affects poor people in tropical, developing countries. Changes in vector-borne disease impacts are often linked to human modification of ecosystems as well as climate change. For tropical ecosystems, the health impacts of future environmental and developmental policy depend on how vector-borne disease risks trade off against other ecosystem services across heterogeneous landscapes. By linking future socio-economic and climate change pathways to dynamic land use models, this study is amongst the first to analyse and project impacts of both land use and climate change on continental-scale patterns in vector-borne diseases. Models were developed for cutaneous and visceral leishmaniasis in the Americas—ecologically complex sand fly borne infections linked to tropical forests and diverse wild and domestic mammal hosts. Both diseases were hypothesised to increase with available interface habitat between forest and agricultural or domestic habitats and with mammal biodiversity. However, landscape edge metrics were not important as predictors of leishmaniasis. Models including mammal richness were similar in accuracy and predicted disease extent to models containing only climate and land use predictors. Overall, climatic factors explained 80% and land use factors only 20% of the variance in past disease patterns. Both diseases, but especially cutaneous leishmaniasis, were associated with low seasonality in temperature and precipitation. Since such seasonality increases under future climate change, particularly under strong climate forcing, both diseases were predicted to contract in geographical extent to 2050, with cutaneous leishmaniasis contracting by between 35% and 50%. Whilst visceral leishmaniasis contracted slightly more under strong than weak management for carbon, biodiversity and ecosystem services, future cutaneous leishmaniasis extent was relatively insensitive to future alternative socio-economic pathways. Models parameterised at narrower geographical scales may be more sensitive to land use pattern and project more substantial changes in disease extent under future alternative socio-economic pathways

Emergence of Community-Associated Methicillin-Resistant Staphylococcus aureus Carriage in Children in Cambodia

We previously described the first reported isolation of methicillin-resistant Staphylococcus aureus (MRSA) (a case series of pediatric community-associated MRSA infections) in Cambodia. We define the rate of pediatric MRSA carriage in the same population and characterize the associated bacterial genotypes by using pulsed-field gel electrophoresis and multilocus sequence typing. A prospective cohort study of MRSA carriage conducted over one month at the Angkor Hospital for Children, Siem Reap, Cambodia, identified MRSA carriage in 87 (3.5%) of 2,485 children who came to the outpatient department, and 6 (4.1%) of 145 inpatients, including at least two with cases of nosocomial acquisition. Genotyping of all 93 MRSA isolates resolved 5 genotypes. Most (91%) isolates were assigned to sequence type 834. Only 28 (32%) of 87 MRSA carriers identified in the outpatient department had no history of recent healthcare contact. The study findings have important implications for healthcare in a setting where diagnostic microbiology and access to antimicrobial drugs with efficacy against MRSA are limited